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Walaiporn Wangchinda, Kanokwan Laohasakprasit, Kanokorn Lerdlamyong, Visanu Thamlikitkul Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Visanu Thamlikitkul, Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand, Tel +66 81-820-6271, Fax +66 2-412-5994, Email visanu.tha@mahidol.ac.thPurpose: To investigate the epidemiology of carbapenem-resistant Enterobacterales (CRE) colonization or CRE infection relative to the natural history and clinical course of CRE colonization or CRE infection in hospitalized patients during admission and after discharge.Material and Methods: Two adult cohorts were enrolled. Cohort I comprised hospitalized patients who had CRE isolated from their clinical specimens during 2018– 2020. CRE colonization or CRE infection was based on the absence/presence of clinical features of infection. Information regarding the natural history and clinical course of these patients was collected during hospitalization. Stool samples were evaluated for CRE once a week during hospitalization, and then once every few months after discharge until negative for CRE. Cohort II comprised patients who had CRE isolated from clinical specimens during hospitalization and who were discharged during 2015– 2018. CRE in stool samples collected from these patients every few months was assessed to determine duration of CRE in stool.Results: CRE in stool was detected in 69.7% of 353 patients in cohort I. K. pneumoniae was the predominant CRE isolated from clinical samples (76.8%) and stool samples (65.7%). Among the 225 CRE-colonized patients, 20.4% developed subsequent CRE infections with a median duration from CRE colonization to CRE infection of 14 days. Among 174 CRE-infected patients, the most common infection was pneumonia with mortality at discharge of 47.7%. Duration of CRE colonization in stool was < 1 year in 50.0% of cohort I patients, and < 2 years in 91.4% of patients in cohort II.Conclusion: CRE isolated from clinical specimens in hospitalized patients are more likely to cause colonization than infection. Patients with CRE colonization are at risk of subsequent CRE infection with high mortality. Stool culture for CRE is needed to verify if contact precautions can be discontinued because the duration of CRE colonization in stool varied from days to years.Keywords: epidemiology, carbapenem-resistant Enterobacterales, infection, colonization, patients, university hospital, Thailand

Chakkraphong Seenama,1,2 Visanu Thamlikitkul,2 Panan Ratthawongjirakul31Program of Molecular Sciences in Medical Microbiology and Immunology, Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand; 2Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Research Group of Innovative Diagnosis of Antimicrobial Resistance, Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, ThailandPurpose: Here, we investigated the genetic relationships and characteristics of extended- spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) isolates from healthy hosts, humans in the community and swine among the livestock of Amphor Mueang, Lamphun Province, Thailand.Patients and methods: Four hundred and nine rectal swabs were collected from healthy people and swine. A total of 212 ESBL-E. coli was isolated and phenotypically confirmed by a combination disk method. Putative ESBL-encoding genes, including blaCTX-M, blaTEM, and blaSHV, were examined by multiplex-PCR. Randomly selected 42 ESBL-E. coli isolates were whole genome sequenced to characterize the ESBL-encoding genes and identify additional antimicrobial resistance genes. The genetic relatedness of 212 ESBL-E. coli was investigated by multilocus sequence typing.Results: Overall, blaCTX-M was the dominant ESBL-encoding gene found in 95.75% of the isolates, followed by blaTEM (60.85%) and blaSHV (2.40%). While blaCTX-M-55 was the most common blaESBL subgroup found in this study. Whole genome sequencing showed a total of 15 different antimicrobial resistance genes other than blaESBL, including sul, qnr, aph(3ʹ)-Ia, among the selected 42 ESBL-E. coli isolates. Over half of the ESBL-E. coli (56.60%) carried blaCTX-M co-existing with blaTEM. The most common sequence types (STs) identified from human isolates were ST131, ST101, and ST70 while those isolated from swine were ST10, ST48, and ST131. ST131 strains carrying blaCTX-M were the major isolated ESBL-E. coli strains, supporting a previous study that considered this strain truly pathogenic. Noticeably, 66.51% of ESBL-E. coli strains shared 19 identical STs, including a host-restricted ST131 between humans and swine, suggesting that transmission between these two hosts might be possible.Conclusion: Proof of a direct transfer of ESBL-E. coli from animals to humans, or vice versa, is required for further elucidation. The ESBL-E. coli isolated from both types of healthy hosts may serve as a reservoir for community-acquired antimicrobial resistance.Keywords: ESBL-E. coli, blaCTX-M, blaTEM, and blaSHV, MLST, genetic relatedness

Thundon Ngamprasertchai,1 Adhiratha Boonyasiri,2 Lantharita Charoenpong,3 Sireethorn Nimitvilai,4 Narisorn Lorchirachoonkul,5 Luksame Wattanamongkonsil,2 Visanu Thamlikitkul6 1Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 2Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Division of Medicine, Chaophraya Yommarat Hospital, Suphanburi, Thailand; 4Division of Medicine, Nakhornpathom Hospital, Nakhornpathom, Thailand; 5Division of Medicine, Ratchaburi Hospital, Ratchaburi, Thailand; 6Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Background: Colistimethate sodium (colistin) has been used in the treatment of infections caused by extensively drug-resistant (XDR) Gram-negative bacteria in Thailand over the past decade, with a mortality rate of 50% and a nephrotoxicity rate of 40%. Polymyxin B has not been available in Thailand. We conducted a Phase II clinical study to determine the effectiveness and safety of polymyxin B, compared with colistin, for the treatment of XDR Gram-negative bacterial infections in Thai patients.Methods: A total of 73 adult patients hospitalized at four participating tertiary care hospitals from January 2015 to December 2015 who had infections caused by XDR Gram-negative bacteria and had to receive colistin were enrolled in the study. Polymyxin B (100 mg/day) was administered intravenously every 12 hours for 7–14 days.Results: Most of the patients were older males with comorbidities who had received antibiotics, particularly carbapenems, prior to receiving polymyxin B. More than half of the patients had pneumonia, and 51.5% of the infections were caused by XDR Acinetobacter baumannii, which was susceptible to colistin. Good clinical responses at the end of treatment were observed in 78.1% of cases, the overall 28-day mortality rate from all causes was 28.7%, the microbiological clearance of the targeted bacteria after therapy was 56.2% and nephrotoxicity occurred in 24.7% of cases. Neurotoxicity relating to reversible numbness was observed in two cases.Conclusion: Polymyxin B seems to be effective and safe for the treatment of XDR Gram-negative bacterial infections. Polymyxin B should be considered as an alternative to colistin for treatment of infections caused by XDR Gram-negative bacteria in Thai adult patients, especially those at risk of nephrotoxicity. Keywords: mortality, acute kidney injury, Acinetobacter baumannii

Purpose: Here, we investigated the genetic relationships and characteristics of extended- spectrum beta-lactamase-producing Escherichia coli (ESBL- E. coli ) isolates from healthy hosts, humans in the community and swine among the livestock of Amphor Mueang, Lamphun Province, Thailand., Patients and Methods: Four hundred and nine rectal swabs were collected from healthy people and swine. A total of 212 ESBL- E. coli was isolated and phenotypically confirmed by a combination disk method. Putative ESBL-encoding genes, including bla CTX-M , bla TEM , and bla SHV , were examined by multiplex-PCR. Randomly selected 42 ESBL- E. coli isolates were whole genome sequenced to characterize the ESBL-encoding genes and identify additional antimicrobial resistance genes. The genetic relatedness of 212 ESBL- E. coli was investigated by multilocus sequence typing., Results: Overall, bla CTX-M was the dominant ESBL-encoding gene found in 95.75% of the isolates, followed by bla TEM (60.85%) and bla SHV (2.40%). While bla CTX-M-55 was the most common bla ESBL subgroup found in this study. Whole genome sequencing showed a total of 15 different antimicrobial resistance genes other than bla ESBL , including sul, qnr, aph(3')-Ia , among the selected 42 ESBL- E. coli isolates. Over half of the ESBL- E. coli (56.60%) carried bla CTX-M co-existing with bla TEM . The most common sequence types (STs) identified from human isolates were ST131, ST101, and ST70 while those isolated from swine were ST10, ST48, and ST131. ST131 strains carrying bla CTX-M were the major isolated ESBL- E. coli strains, supporting a previous study that considered this strain truly pathogenic. Noticeably, 66.51% of ESBL- E. coli strains shared 19 identical STs, including a host-restricted ST131 between humans and swine, suggesting that transmission between these two hosts might be possible., Conclusion: Proof of a direct transfer of ESBL- E. coli from animals to humans, or vice versa, is required for further elucidation. The ESBL- E. coli isolated from both types of healthy hosts may serve as a reservoir for community-acquired antimicrobial resistance., Competing Interests: The authors declare that they have no conflicts of interest related to the publication of this article.