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Polymyxin B (PMB) has reemerged as a last‐line therapy for infections caused by multidrug‐resistant gram‐negative pathogens, but dosing is challenging because of its narrow therapeutic window and pharmacokinetic (PK) variability. Population PK (POPPK) models based on suitably powered clinical studies with appropriate sampling strategies that take variability into consideration can inform PMB dosing to maximize efficacy and minimize toxicity and resistance. Here we reviewed published PMB POPPK models and evaluated them using an external validation data set (EVD) of patients who are critically ill and enrolled in an ongoing clinical study to assess their utility. Seven published POPPK models were employed using the reported model equations, parameter values, covariate relationships, interpatient variability, parameter covariance, and unexplained residual variability in NONMEM (Version 7.4.3). The predictive ability of the models was assessed using prediction‐based and simulation‐based diagnostics. Patient characteristics and treatment information were comparable across studies and with the EVD (n = 40), but the sampling strategy was a main source of PK variability across studies. All models visually and statistically underpredicted EVD plasma concentrations, but the two‐compartment models more accurately described the external data set. As current POPPK models were inadequately predictive of the EVD, creation of a new POPPK model based on an appropriately powered clinical study with an informed PK sampling strategy would be expected to improve characterization of PMB PK and identify covariates to explain interpatient variability. Such a model would support model‐informed precision dosing frameworks, which are urgently needed to improve PMB treatment efficacy, limit resistance, and reduce toxicity in patients who are critically ill.

Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

During the COVID-19 pandemic, distinguishing dengue from cases of COVID-19 in endemic areas can be difficult. In a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, where enhanced personal protective equipment was used by healthcare workers until COVID-19 was ruled out. From January to May 2020, 11,086 admissions were screened for COVID-19; 868 cases of COVID-19 were diagnosed in our institution, along with 380 cases of dengue. Only 8.5% (943/11,086) of suspected COVID-19 cases were concurrently tested for dengue serology due to a compatible overlapping clinical syndrome, and dengue was established as an alternative diagnosis in 2% (207/10,218) of suspected COVID-19 cases that tested negative. There were eight COVID-19 cases with likely false-positive dengue serology and one probable COVID-19/dengue coinfection. From April to May 2020, 251 admissions presenting as viral prodromes with no respiratory symptoms were screened; of those, 15 cases had COVID-19, and 2/15 had false-positive dengue IgM. Epidemiology investigations showed no healthcare-associated transmission. In a dengue epidemic season coinciding with a COVID-19 pandemic, dengue was established as an alternative diagnosis in a minority of COVID-19 suspects, likely due to early availability of basic diagnostics. Routine screening of patients with viral prodromes during a dual outbreak of COVID-19 and dengue enabled containment of COVID-19 cases masquerading as dengue with false-positive IgM.

During this coronavirus disease 2019 (COVID-19) pandemic, physicians have the important task of risk stratifying patients who present with acute respiratory illnesses. Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections. Thus, identifying clinical features that are strongly associated with COVID-19 in comparison to other respiratory viruses can aid risk stratification and testing prioritization especially in situations where resources for virological testing and resources for isolation facilities are limited. In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups. In comparing outcomes, patients with COVID-19 were more likely to need high dependency or intensive care unit care and had a longer median length of stay. With our findings, we emphasize that epidemiological risk factors and clinical symptoms are more useful than laboratory and radiological abnormalities in differentiating COVID-19 from other respiratory viral infections.

The SARS-CoV-2 pandemic is rapidly evolving and remains a major health challenge worldwide. With an increase in pregnant women with COVID-19 infection, we recognized an urgent need to set up a multidisciplinary taskforce to provide safe and holistic care for this group of women. In this review of practice in a tertiary hospital in Singapore, we discuss the key considerations in setting up an isolation maternity unit and our strategies for peripartum and postpartum care. Through teleconsultation, we involve these women and their families in the discussion of timing and mode of birth, disposition of babies after birth and safety of breastfeeding to enable them to make informed decisions and individualize their care.

The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010-2015 and discovered 18 isolates from 7 patients also harbored hypervirulence features. All isolates contained a closely related plasmid (pKPC2) harboring blaKPC-2, a K. pneumoniae carbapenemase gene, and had a hypervirulent background of capsular serotypes K1, K2, and K20. In total, 5 of 7 first patient isolates were hypermucoviscous, and 6 were virulent in mice. The pKPC2 was highly transmissible and remarkably stable, maintained in bacteria within a patient with few changes for months in the absence of antimicrobial drug selection pressure. Intrapatient isolates were also able to acquire additional antimicrobial drug resistance genes when inside human bodies. Our results highlight the potential spread of carbapenem-resistant hypervirulent K. pneumoniae in Singapore. National Medical Research Council (NMRC) Published version This work was supported by the National University of Singapore, Yong Loo Lin School of Medicine Aspiration Fund (NUHSRO/2014/068/AF New Idea/03), and National Medical Research Council (NMRC) collaborative grant Collaborative Solutions Targeting Antimicrobial Resistance Threats in Health Systems (CoSTAR-HS, HS/ARGSeedGrant/2017/03) to Y.-H.G. Additional grant support was provided by CoSTAR-HS (NMRC CGAug16C005), NMRC Clinician Scientist Award (NMRC/CSA-INV/0007/2016), and NMRC Clinician Scientist Award (MOH-000276).

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.

Background In early months of COVID-19 pandemic, SGH recorded a year-on-year increase in antibiotic (ABx) use for community acquired acute respiratory infection (CA ARI) from Feb-Apr 2019 (48.7 defined daily doses (DDD)/100 bed-days) to 2020 (50.8 DDD/100 bed-days). To address concerns of misuse, the antibiotic stewardship unit (ASU) expanded prospective audit feedback (PAF) to CA ARI patients admitted to ARI wards, with low procalcitonin (PCT). PAF was conducted on day 2-3 of ABx, on weekdays. Doctors received feedback to stop/modify when ABx was deemed inappropriate. Here, we describe the impact of ASU’s adaptive approach to curb rising ABx use in patients admitted for ARI during COVID-19 pandemic. Methods A Pre- & Post-intervention study was conducted. All patients started on ABx (ceftriaxone/co-amoxiclav/piptazo/carbapenems/levofloxacin) for CA ARI & PCT < 0.5µg/L were analysed. Those who died ≤48h of admission; admitted to intensive care; required ABx escalation; >1 infective sites; complex lung infection were excluded. Primary objective was to compare the proportion of ABx stopped ≤4 days (time to final infection diagnosis) Pre (22/3-18/4/20) & Post (21/4-13/7/20). Results 184 (Pre) & 528 (Post) ABx courses were analysed. ASU audited 51 (Pre) & 380 (Post) courses with the rest discontinued/discharged before review. Patients were largely similar in both periods; a third had low likelihood of bacterial infection (C reactive protein < 30mg/L). In Post, 73 feedback was given to stop ABx (often because symptoms suggested viral/fluid overload) & 18 to switch to oral ABx. 82 (90%) feedback was accepted. No ABx was restarted ≤48h or deaths ≤30 days due to ARI. 1 patient had C. difficile diarrhoea a day after ABx cessation as per ASU feedback. Proportion of all ABx stopped ≤4 days was higher in Post than Pre [27/184 (15%) vs 152/528 (29%), p< 0.01]. Median duration of therapy of IV ABx was reduced (6.5 vs 3 days, p< 0.01), with corresponding shorter median length of stay (10.5 vs 6 days, p< 0.01). Conclusion PAF directly and indirectly reduced ABx duration in patients treated for CA ARI as prescribers become more conscious about stopping ABx when investigations show low likelihood of bacterial infection. ASU must remain agile during pandemics to detect emerging problems and adapt processes to counter early. Disclosures All Authors: No reported disclosures

Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration–time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing.

ObjectiveTo determine the clinical outcomes of older COVID-19 patients who received DMB compared to those who did not. We hypothesized that fewer patients administered DMB would require oxygen therapy and/or intensive care support than those who did not.MethodologyCohort observational study of all consecutive hospitalized COVID-19 patients aged 50 and above in a tertiary academic hospital who received DMB compared to a recent cohort who did not. Patients were administered oral vitamin D3 1000 IU OD, magnesium 150mg OD and vitamin B12 500mcg OD (DMB) upon admission if they did not require oxygen therapy. Primary outcome was deterioration post-DMB administration leading to any form of oxygen therapy and/or intensive care support.ResultsBetween 15 January and 15 April 2020, 43 consecutive COVID-19 patients aged ≥50 were identified. 17 patients received DMB and 26 patients did not. Baseline demographic characteristics between the two groups was significantly different in age. In univariate analysis, age and hypertension showed significant influence on outcome while DMB retained protective significance after adjusting for age or hypertension separately in multivariate analysis. Fewer DMB patients than controls required initiation of oxygen therapy during their hospitalization (17.6% vs 61.5%, P=0.006). DMB exposure was associated with odds ratios of 0.13 (95% CI: 0.03 – 0.59) and 0.20 (95% CI: 0.04 – 0.93) for oxygen therapy and/or intensive care support on univariate and multivariate analyses respectively.ConclusionsDMB combination in older COVID-19 patients was associated with a significant reduction in proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support. This study supports further larger randomized control trials to ascertain the full benefit of DMB in ameliorating COVID-19 severity.

Objective Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. This study aims to describe the thrombotic and bleeding rates in COVID-19 patients admitted to intensive care units (ICU) in Singapore. Design Retrospective observational study involving all consecutive adult COVID-19 patients who required ICU admission between 23 January 2020 and 30 April 2020. Setting National multicenter study involving all eight public hospitals in Singapore. Patients 111 consecutive COVID-19 patients who required ICU admission were included. Measurements and Main Results Primary outcome was any venous or arterial thrombotic events occurred in ICU. Other measures included (1) the overall, venous and arterial thrombotic events throughout the hospitalisation, (2) major and minor bleeding events. The overall thrombotic rate in ICU was 11.7% (n=13), with 1.8% (n=2) venous and 9.9% (n=11) arterial events. The overall thrombotic rates throughout hospitalisation, censored at 30 April 2020, increased to 18.0% (n=20) with 6.3% (n=7) venous and 11.7% (n=13) arterial events. Major and minor bleeding rates were 14.8% (n=16) and 3.7% (n=4), respectively. Two-third of the patients received pharmacological thromboprophylaxis in ICU. Conclusions Critically ill COVID-19 patients in Singapore have lower VTE but higher arterial thrombosis rates with higher bleeding manifestations than other reported cohorts. Standard thromboprophylaxis may be sufficient to prevent thrombotic complications in patients with similar demographics. Disclosures No relevant conflicts of interest to declare.

Highlights • During the COVID-19 outbreak, antibiotic use has increased, especially respiratory antibiotics. • Healthcare resources are diverted to containment and management of COVID-19 cases, but the efforts of antibiotic stewardship programmes (ASPs) must run in parallel to mitigate antibiotic misuse and antimicrobial resistance. • ASPs must be operationally adaptable, and possess robust surveillance systems that detect subtle changes in prescribing and resistance trends. • This is an opportunity to execute a syndromic approach to guide antibiotic prescribing. • Continued engagement and education of prescribers to ensure appropriate prescription of antibiotics is important., Healthcare resources are being diverted for the containment and control of coronavirus disease 2019 (COVID-19). During this outbreak, it is cautioned that antibiotic misuse may be increased, especially for respiratory tract infections. With stewardship interventions, the duration of antibiotic therapy and length of stay of hospitalized patients can be reduced significantly. Antibiotic stewardship programmes should continually engage and educate prescribers to mitigate antibiotic misuse during the COVID-19 pandemic.

Background Information on non-tuberculosis mycobacterial (NTM) diseases remains limited in Singapore and other Southeast Asian countries. This study aimed to delineate epidemiological and clinical features of pulmonary NTM disease. Methods A retrospective review was performed on all NTM isolates identified in Singapore General Hospital from 2012 to 2016 using the 2007 ATS/IDSA diagnostic criteria. Results A total of 2026 NTM isolates from 852 patients were identified. M. abscessus-chelonae group (1010, 49.9%) was the most commonly isolated and implicated in pulmonary NTM disease. Pulmonary cases (352, 76%) had the highest prevalence among patients diagnosed with NTM diseases (465/852, 54.6%) with no gender difference. Male patients were older (68.5 years, P = 0.014) with a higher incidence of chronic obstructive pulmonary disease (COPD) (23.6%, P

Highlights • Use of a combination of vitamin D, magnesium, and vitamin B12 (DMB) in patients with coronavirus disease (COVID-19) was studied. • Fewer patients ≥50 y of age with COVID-19 on DMB suffered clinical deterioration. • Further studies are warranted to ascertain the full benefit of DMB in patients with COVID-19., Objectives The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. Methods This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. Results Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03–0.59) and 0.20 (95% CI, 0.04–0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. Conclusions A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

We report a case of a hospitalised patient with COVID-19 who developed subacute thyroiditis in association with SARS-COV-2 infection. The patient presented with tachycardia, anterior neck pain and thyroid function tests revealing hyperthyroidism together with consistent ultrasonographic evidence suggesting subacute thyroiditis. Treatment with corticosteroids resulted in rapid clinical resolution. This case illustrates that subacute thyroiditis associated with viruses such as SARS-CoV-2 should be recognised as a complication of COVID-19 and considered as a differential diagnosis when infected patients present with tachycardia without evidence of progression of COVID-19 illness.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P

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 100000 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 100000 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.

Summary Background Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever. Methods To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21–65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01619969. Findings We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (–1·86, SD 1·07) than in the placebo group (–1·64, 0·75), but the difference was non-significant (–0·22, 90% CI −0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16–26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups. Interpretation Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue. Funding STOP Dengue Translational Clinical Research.

Objectives Owing to gene transposition and plasmid conjugation, New Delhi metallo-β-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore. Methods Thirty-three Enterobacteriaceae isolates (collection years 2010-14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147. Results In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link. Conclusions A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs.