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The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)- block -poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections. The authors report the synthesis of an enantiomeric block co-beta-peptide that kills methicillin-resistant Staphylococcus aureus , including biofilm and persister bacterial cells, and disperses biofilms. The copolymer displays antibacterial activity in human ex vivo and mouse in vivo infection models without toxicity.

Objectives: Plasmid-mediated AmpC beta-lactamases represent a growing clinical concern in Enterobacterales, with challenges in diagnostic approaches, limited data on clinical outcomes, and our incomplete understanding of their regulatory mechanisms warranting the need for further investigation. Methods: This retrospective study examined the genomic and clinical characteristics of cefoxitin-non-susceptible, ceftriaxone-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates collected from a tertiary hospital in Singapore. Whole-genome sequencing was performed to detect ampC genes, subtypes, and associated regulatory elements. Results: Among 108 cefoxitin-non-susceptible isolates, only 15 (13.9%) harboured plasmid-mediated ampC, suggesting that cefoxitin non-susceptibility alone in ceftriaxone susceptible isolates was not predictive of ampC carriage. All plasmid-ampC isolates were from the blaDHA-1 subtype and carried ampR, a known transcriptional regulator of inducible beta-lactamase expression. Notably, five non-ampC carrying Klebsiella isolates displayed truncations in ompK35 and ompK36, which could potentially contribute to reduced cefoxitin susceptibility via porin loss. Conclusions: These findings underscore the limited diagnostic utility of cefoxitin susceptibility testing for detecting plasmid-mediated ampC producers and highlight the clinical relevance of regulatory genes such as ampR in mediating inducible resistance. The routine incorporation of molecular diagnostics or genome sequencing may be necessary to improve detection accuracy and inform antimicrobial stewardship strategies.

Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness ( p  = 0.01, χ 2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2. Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

Objectives: Over the past 2 years, many infection prevention and control (IPC) resources have been diverted to manage the COVID-19 pandemic. Its impact on the incidence of antimicrobial-resistant organisms has not been adequately studied. We investigated the impact of the pandemic on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore. Methods: We extracted data on unique CRE isolates (clinical and/or surveillance cultures) and patient days for 6 public hospitals in Singapore from the carbapenemase-producing Enterobacteriaceae (CaPES) study group database, and we calculated the monthly incidence of CRE (per 10,000 patient days). Interrupted time-series (ITS) analysis was conducted with the pre–COVID-19 period defined as before February 2020, and the COVID-19 period defined as after February 2020. Statistical analyses were performed using Stata version 15 software. Results: From January 2017 to March 2021, 6,770 CRE isolates and 9,126,704 patient days were documented. The trend in CRE monthly incidence increased significantly during the pre–COVID-19 period (0.060; 95% CI, 0.033–0.094; P < .001) but decreased during the COVID-19 period (−0.183; 95% CI, −0.390 to 0.023; P = .080) without stepwise change in the incidence (−1.496; 95% CI, −3.477 to 0.485; P = .135). The trend in monthly incidence rate of CRE clinical cultures increased significantly during the pre–COVID-19 period (0.046; 95% CI, 0.028–0.064; P < .001) and decreased significantly during COVID-19 period (−0.148; 95% CI, −0.249 to −0.048; P = .048) with no stepwise change in the incidence (−0.063; 95% CI, −0.803 to 0.677; P = .864). The trend in monthly incidence rate of CRE surveillance cultures decreased during the pre–COVID-19 period (−0.020; 95% CI, −0.062 to 0.022; P = .341) and the COVID-19 period (−0.067; 95% CI, −0.291to 0.158; P = .552) without stepwise change in the incidence (−1.327; 95% CI, −3.535 to 0.881; P = .233). Conclusions: The rate of CRE in clinical cultures decreased during COVID-19 but not the rate in surveillance cultures. Further studies are warranted to study the impact of COVID-19 on CREs. (DUPLICATE DELETED)

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients’ admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination. Carbapenemase-producing Enterobacterales cause healthcare-associated infections but modes of transmission are not well understood. Here, the authors find evidence of transmission without direct patient contact, indicating presence of undetected environmental reservoirs, whilst half of the transmission events are likely due to plasmid-mediated transmission.

An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus infection in Asia. In the first phase of the outbreak, patients with suspected Zika virus infection were isolated in two national referral hospitals until their serum tested negative for the virus. Enhanced vector control and community engagement measures were deployed in disease clusters, including stepped-up mosquito larvicide and adulticide use, community participation in source reduction (destruction of mosquito breeding sites), and work with the local media to promote awareness of the outbreak. Clinical and epidemiological data were collected from patients with confirmed Zika virus infection during the first phase. In the second phase, admission into hospitals for isolation was stopped but vector control efforts continued. Mosquitoes were captured from areas with Zika disease clusters to assess which species were present, their breeding numbers, and to test for Zika virus. Mosquito virus strains were compared with human strains through phylogenetic analysis after full genome sequencing. Reproductive numbers and inferred dates of strain diversification were estimated through Bayesian analyses. From Aug 27 to Nov 30, 2016, 455 cases of Zika virus infection were confirmed in Singapore. Of 163 patients with confirmed Zika virus infection who presented to national referral hospitals during the first phase of the outbreak, Zika virus was detected in the blood samples of 97 (60%) patients and the urine samples of 157 (96%) patients. There were 15 disease clusters, 12 of which had high Aedes aegypti breeding percentages. Captured mosquitoes were pooled into 517 pools for Zika virus screening; nine abdomen pools (2%) were positive for Zika virus, of which seven head and thorax pools were Zika-virus positive. In the phylogenetic analysis, all mosquito sequences clustered within the outbreak lineage. The lineage showed little diversity and was distinct from other Asian lineages. The estimated most recent common ancestor of the outbreak lineage was from May, 2016. With the deployment of vector control and community engagement measures, the estimated reproductive number fell from 3·62 (95% CI 3·48–3·77) for July 31 to Sept 1, 2016, to 1·22 (95% CI 1·19–1·24) 4 weeks later (Sept 1 to Nov 24, 2016). The outbreak shows the ease with which Zika virus can be introduced and spread despite good baseline vector control. Disease surveillance, enhanced vector control, and community awareness and engagement helped to quickly curb further spread of the virus. These intensive measures might be useful for other countries facing the same threat. National Medical Research Council Singapore, Centre for Infectious Disease Epidemiology and Research, and A*STAR Biomedical Research Council.

Background. Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. Methods. Quarterly incidence of unique subjects (per 100 000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. Results. Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100 000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67–6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10–7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. Conclusions. Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.

The ST131 multilocus sequence type (MLST) of Escherichia coli is a globally successful pathogen whose dissemination is increasing rates of antibiotic resistance. Numerous global surveys have demonstrated the pervasiveness of this clone; in some regions ST131 accounts for up to 30% of all E . coli isolates. However, many regions are underrepresented in these published surveys, including Africa, South America, and Asia. We collected consecutive bloodstream E . coli isolates from three countries in Southeast Asia; ST131 was the most common MLST type. As in other studies, the C2/H30Rx clade accounted for the majority of ST131 strains. Clinical risk factors were similar to other reported studies. However, we found that nearly all of the C2 strains in this study were closely related, forming what we denote the SEA-C2 clone. The SEA-C2 clone is enriched for strains from Asia, particularly Southeast Asia and Singapore. The SEA-C2 clone accounts for all of the excess resistance and virulence of ST131 relative to non-ST131 E . coli . The SEA-C2 strains appear to be locally circulating and dominant in Southeast Asia, despite the intuition that high international connectivity and travel would enable frequent opportunities for other strains to establish themselves.

Plasmid-mediated transmission can account for half of carbapenem-producing Enterobacterales (CPE) dissemination, underscoring the need to identify genetic determinants of plasmid persistence in the hospital setting. From 1,088 CPE isolates detected through nationwide surveillance in Singapore over five years, 1,115 closed carbapenemase-producing plasmids were identified and clustered, of which 92.5% ( n  = 1031) were grouped into 48 plasmid clusters (PCs). The most common plasmid genotypes were PC1 and PC2. Of 389 isolates carrying bla KPC-2 -positive PC1 plasmids and 283 isolates carrying bla NDM-1 -positive PC2 plasmids, 236 (60.7%) and 168 (59.4%) putatively acquired the carbapenemase gene via plasmid-mediated horizontal transmission, whereas 153 (39.3%) and 115 (40.6%) putatively acquired the carbapenemase gene via clonal lineage-dependent vertical transmission, respectively. Less abundant plasmids showed distinct inserted genomic regions encoding genes related to heavy metal and formaldehyde detoxification not found in predominant plasmids. Our data suggest that PC1 and PC2 genotypes are better adapted for stable propagation of bla KPC-2 and bla NDM-1 , respectively, during inter-patient clonal spread and across multiple species (and sequence types) compared to other genetic settings. We propose that a crucial factor enabling evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population is the maintenance of conserved genomes, thus minimizing fitness costs to their hosts. Plasmid-mediated transmission plays a significant role in the spread of carbapenem-resistant Enterobacterales. Here, analyzing 1,115 carbapenemase-producing plasmids from Singapore, the authors suggest that maintenance of conserved genomes adapted for stable propagation across multiple species, enables evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population.