Increasing International Collaboration and Networking Among High-level Isolation Units and Programs

Peer Reviewe

Genomic identification of two Phytobacter diazotrophicus isolates from a neonatal intensive care unit in Singapore

We report the draft genome sequences of two Phytobacter diazotrophicus isolates recovered from a swab specimen from the water faucet located in the Neonatal Intensive Care Unit (ICU), National University Hospital, Singapore. The isolates were misidentified as Cronobacter sakazakii and Klebsiella oxytoca using biochemical methods. Whole-genome sequencing (WGS) was performed to determine their identity

Correction for Hon et al., “Genomic Identification of Two Phytobacter diazotrophicus Isolates from a Neonatal Intensive Care Unit in Singapore”

Author correction for https://doi.org/10.1128/mra.00167-2

Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in South-East Asia

Bloodstream infections (BSIs) are a leading cause of sepsis, a life-threatening condition that contributes significantly to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside- and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections. Here, we collected a panel of 470 MDR GNB isolates from health care facilities in Cambodia, Laos, Singapore, Thailand, and Vietnam for a multi-centre assessment of their antimicrobial susceptibility to apramycin in comparison to other aminoglycosides and colistin by broth microdilution assays. Apramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem- and third-generation cephalosporin (3GC) resistant Enterobacterales, all Acinetobacter baumannii, and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, only four (6.2%) had an apramycin MIC > 16 µg/mL. Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, 3GC, and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of multidrug-resistant BSIs. Keywords: Bloodstream infection; Gram negative; aminoglycoside; antimicrobial resistance; apramycin; blood culture isolates

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest

Susceptibility Testing for the Polymyxins: Two Steps Back, Three Steps Forward?

Optimizing and standardizing susceptibility testing for the polymyxins have become pressing issues, given the rise in multidrug-resistant Gram-negative bacilli. Recently, both the CLSI and EUCAST have recommended broth microdilution (BMD) (without polysorbate) as the reference method for polymyxin susceptibility testing. In this issue, K. L. Chew et al. (J Clin Microbiol 55:2609–2616, 2017, https://doi-org.ezlibproxy1.ntu.edu.sg/10.1128/JCM.00268-17) compare the performances of three commercial BMD panels and the Etest to the reference, BMD, for polymyxin B and colistin, using 76 Enterobacteriaceae isolates (21 of which were mcr-1 positive). Although none of the commercial BMD panels strictly met FDA performance standards in this evaluation, possibly because of the small number isolates tested, the Sensititre panel achieved >90% categorical agreement for both polymyxin compounds. These results also reaffirm CLSI and EUCAST guidance that gradient diffusion testing, which had unacceptable error rates, should be abandoned. In a simulated analysis with lowered breakpoints (susceptible, ≤1 mg/liter; intermediate, 2 mg/liter; resistant, ≥4 mg/liter), error rates and agreement were improved across the various methods and the rate of detection of mcr-1-positive isolates improved. These observations, taken together with recent pharmacokinetic data on optimizing target attainment for the polymyxins, suggest that more-stringent (lower) breakpoints may be reasonable, although such an approach may be limited by the inherent reliability of current testing methodologies and a lack of robust clinical correlative data, which are sorely needed.Published versio

COVID-19 - where do we go from here?

The cluster of viral pneumonia cases that first began in Wuhan, Hubei province, China, in December 2019 has rapidly spread within China and globally. The virus responsible was subsequently identified on 7 January 2020 and the infection was given the official name of coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on 11 February 2020. The first imported case of COVID-19 infection in Singapore was reported on 23 January 2020, the day on which all forms of travel into and out of Wuhan city were prohibited. As of 21 February 2020, 77,691 COVID-19 cases and 2,362 deaths had been reported worldwide. This skyrocketed to 617,548 cases as of 28 February 2020, with 732 cases in Singapore.Published versio

Urinary Tract Infections due to MultidrugResistant Enterobacteriaceae: Prevalence and Risk Factors in a Chicago Emergency Department. Emergency Medicine International2013; 2013

Background. Selection of empiric antibiotics for urinary tract infections (UTIs) has become more challenging because of the increasing rates of multidrug-resistant Enterobacteriaceae (MDRE) infections. Methods. This retrospective study was conducted to determine antibiotic resistance patterns, risk factors, and appropriate empiric antibiotic selection for MDRE UTIs. Adult patients seen in the Emergency Department (ED) with Enterobacteriaceae UTIs during 2008-2009 were identified from review of microbiology records. MDRE were defined as organisms resistant to at least 3 categories of antibiotics. Results. There were 431 eligible patients; 83 (19%) had MDRE UTIs. Resistance rates for individual antibiotics among MDRE UTIs were significantly greater than non-MDRE UTIs: levofloxacin, 72% versus 14%; TMP-SMX, 77% versus 12%; amoxicillin-clavulanate, 35% versus 4%; nitrofurantoin, 21% versus 12%, and ceftriaxone, 20% versus 0%. All Enterobacteriaceae isolates were susceptible to ertapenem (MIC ≤ 2 mg/L). Independent risk factors for MDRE UTI were prior fluoroquinolone use within 3 months (adjusted odds ratio (aOR) 3.64; = 0.001), healthcareassociated risks (aOR 2.32; = 0.009), and obstructive uropathy (aOR 2.22; = 0.04). Conclusion. Our study suggests that oncedaily intravenous or intramuscular ertapenem may be appropriate for outpatient treatment of ED patients with MDRE UTI