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• W4361248653 abstract "We read with great interest the article by La et al. describing an increased occurrence of the most problematic multi-drug resistant (MDR) organisms after coronavirus disease 2019 (COVID-19) pandemic in South Korea.1La Y. Hong J.Y. Lee H.S. Lee E.H. Lee K.H. Song Y.G. et al.Increase of multidrug-resistant bacteria after the COVID-19 pandemic in South Korea: time-series analyses of a long-term multicenter cohort.J Infect. 2022; 85: 702-769Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Interestingly, the MDR-Acinetobacter baumannii and -Pseudomonas aeruginosa, which had been steadily decreasing before the pandemic, demonstrated an increasing trend in patients with bacteremia after COVID-19.1La Y. Hong J.Y. Lee H.S. Lee E.H. Lee K.H. Song Y.G. et al.Increase of multidrug-resistant bacteria after the COVID-19 pandemic in South Korea: time-series analyses of a long-term multicenter cohort.J Infect. 2022; 85: 702-769Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Burkholderia pseudomallei, a facultative intracellular gram-negative bacterium, causes melioidosis, a life-threatening and multi-syndrome illness, in humans.2Bzdyl N.M. Moran C.L. Bendo J. Sarkar-Tyson M. Pathogenicity and virulence of Burkholderia pseudomallei.Virulence. 2022; 13: 1945-1965Crossref PubMed Scopus (2) Google Scholar Melioidosis is widely present in countries across the tropics, especially in Southeast Asia and northern Australia.3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar In Taiwan, the average incidence rate of melioidosis was 0.6 per 100,000 person-years from 2004 to 2010, which was relatively low when compared with northeast Thailand (12.7 per 100,000 person-years) and northern Australia (19.6 per 100,000 person-years).4Chen Y.L. Lin Y.C. Chen Y.S. Chen S.C. Liu Y.M. Tseng I.L. et al.Characterisation of predominant molecular patterns of Burkholderia pseudomallei in Taiwan.Trans R Soc Trop Med Hyg. 2013; 107: 165-169Crossref PubMed Scopus (15) Google Scholar According to data from the Notifiable Infectious Diseases Statistics System in the Taiwan Centers for Disease Control, there were 34.6 cases in average per year reported between 2007 and 2019 and a decline (22 cases) of reported cases in average per year during the pandemic of COVID-19 in 2020–2022 (https://nidss.cdc.gov.tw/) (Fig. 1). Antibiotic treatment for this infection included two phases: initial intensive therapy for up to 14 days and eradication therapy for at least three months.3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar, 5Rhodes K.A. Schweizer H.P. Antibiotic resistance in Burkholderia species.Drug Resist Updat. 2016; 28: 82-90Crossref PubMed Scopus (186) Google Scholar Ceftazidime, meropenem, and trimethoprim-sulfamethoxazole are common choices for melioidosis treatment.3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar, 4Chen Y.L. Lin Y.C. Chen Y.S. Chen S.C. Liu Y.M. Tseng I.L. et al.Characterisation of predominant molecular patterns of Burkholderia pseudomallei in Taiwan.Trans R Soc Trop Med Hyg. 2013; 107: 165-169Crossref PubMed Scopus (15) Google Scholar However, B. pseudomallei is intrinsically resistant to various antibiotics, such as penicillin, ampicillin, cephalosporins, gentamicin, tobramycin, and streptomycin.3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar Complicated drug resistance mechanisms have been reported.5Rhodes K.A. Schweizer H.P. Antibiotic resistance in Burkholderia species.Drug Resist Updat. 2016; 28: 82-90Crossref PubMed Scopus (186) Google Scholar, 6Sarovich D.S. Webb J.R. Pitman M.C. Viberg L.T. Mayo M. Baird R.W. et al.Raising the stakes: loss of efflux pump regulation decreases meropenem susceptibility in Burkholderia pseudomallei.Clin Infect Dis. 2018; 67: 243-250Crossref PubMed Scopus (28) Google Scholar We report a case of melioidosis with bacteremic community-acquired pneumonia and emergence of drug resistance in Taiwan. This case involved a 78-year-old male with a history of type 2 diabetes mellitus and chronic kidney disease. He had intermittent fever and productive cough with yellowish sputum for 2 days. He visited our Emergency Department in September 2022. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT PCR) (cobas SARS-CoV-2 & Influenza A/B, Roche Molecular Systems, Inc., Pleasanton, CA, U.S. A) was negative. Chest radiograph revealed ground-glass opacity lesions over the left upper lobe (Fig. 2A). He was admitted to the chest medicine ward for community-acquired pneumonia. Antibiotic treatment with cefmetazole 2 g every 8 h (Day 1 to Day 4) was initiated. However, two sets of blood cultures collected on Day 1 yielded Burkholderia pseudomallei on Day 4 (isolate CMUH-BP250-1), as identified by matrix-assisted laser desorption/ionization time-off light mass spectrometry (Bruker Biotyper; Bruker Daltonics GmbH, Bremen, Germany). The time to detection (TTD) of blood culture was 22 h 57 min. Susceptibility tests for B. pseudomallei indicated susceptibility to ceftazidime (minimum inhibitory concentration [MIC], 4 mg/L), levofloxacin (≤1 mg/L), meropenem (2 mg/L), minocycline (≤1 mg/L), and trimethoprim/sulfamethoxazole (1/19 mg/L) using an automatic Phoenix system (Becton-Dickinson Microbiology Systems, Sparks, MD, USA). Therefore, we shifted the antibiotic to intravenous levofloxacin 500 mg per day (Days 4–14). His fever subsided rapidly on Day 5 after levofloxacin use. Nevertheless, ensuing chest radiograph revealed progressive left lung infiltration. Oral azithromycin 250 mg per day was prescribed (Day 11 to Day 14) for immunomodulation. On Day 13, the patient had acute dyspnea and new fever up to 39.4 °C. A chest radiograph revealed bilateral lung infiltration (Fig. 2B). Because the patient chose palliative care with do-not-rescue, no intubation was performed. The patient expired on Day 14. Two sets of blood cultures collected on Day 13 again yielded B. pseudomallei (CMUH-BP250-2) on Day 17, the TTD was 21 h 35 min, and the susceptibility results changed from susceptible to resistant to levofloxacin (MIC,> 4 mg/L), and meropenem (> 4 mg/L). MICs of the other three agents tested for the CMUH-BP250–2 isolate remained the same. To understand the mechanisms of levofloxacin and meropenem resistance, mutations in gyrA and amrR were investigated. Mutations in gyrA are one of the major mechanisms of resistance to fluoroquinolones in Gram-negative bacteria, with most mutations affecting quinolone resistance-determining regions (QRDRs).5Rhodes K.A. Schweizer H.P. Antibiotic resistance in Burkholderia species.Drug Resist Updat. 2016; 28: 82-90Crossref PubMed Scopus (186) Google Scholar Loss of regulation of the resistance-nodulation-division (RND) efflux pump AmrAB-OprA is associated with decreased meropenem susceptibility in B. pseudomallei.6Sarovich D.S. Webb J.R. Pitman M.C. Viberg L.T. Mayo M. Baird R.W. et al.Raising the stakes: loss of efflux pump regulation decreases meropenem susceptibility in Burkholderia pseudomallei.Clin Infect Dis. 2018; 67: 243-250Crossref PubMed Scopus (28) Google Scholar Mutations in amrR, a regulator of the AmrAB-OprA efflux pump, have been identified, leading to high-level meropenem resistance.6Sarovich D.S. Webb J.R. Pitman M.C. Viberg L.T. Mayo M. Baird R.W. et al.Raising the stakes: loss of efflux pump regulation decreases meropenem susceptibility in Burkholderia pseudomallei.Clin Infect Dis. 2018; 67: 243-250Crossref PubMed Scopus (28) Google Scholar PCR followed by sequencing was performed with primer pairs targeting the QRDR of gyrA (gyrAs and gyrAas) and full-length amrR (amrR_Fullgene_F and amrR_Fullgene_R).7Webb J.R. Price E.P. Somprasong N. Schweizer H.P. Baird R.W. Currie B.J. et al.Development and validation of a triplex quantitative real-time PCR assay to detect efflux pump-mediated antibiotic resistance in Burkholderia pseudomallei.Future Microbiol. 2018; 13: 1403-1418Crossref PubMed Scopus (5) Google Scholar Compared with CMUH-BP250–1, the results showed that CMUH-BP250–2 expresses an amino acid substitution in GyrA at position 81 (Gly81Asp). Gly81Asp has been reported in levofloxacin-resistant Burkholderia cepacia complex isolates.8Tseng S.P. Tsai W.C. Liang C.Y. Lin Y.S. Huang J.W. Chang C.Y. et al.The contribution of antibiotic resistance mechanisms in clinical Burkholderia cepacia complex isolates: an emphasis on efflux pump activity.PLoS One. 2014; 9e104986Crossref Scopus (37) Google Scholar A 189-bp (position 267–455) deletion in amrR causing a 66 a.a. (92–154) deletion of AmrR was also found in CMUH-BP250-2 isolate. Whole genome sequencing was carried out on a PacBio Sequel II system (PacBio, Menlo Park, CA, USA). These reads were then used for assembling and polishing of the genome with hifiasm v0.15.3 and GCpp v2.0.2 (https://github.com/PacificBiosciences/gcpp), respectively.9Bureros K.J. Chiu Y.C. Liou C.Y. Ma C.Y. Wang L.C. Complete genome sequence of a suckermouth catfish outbreak isolate, Aeromonas hydrophila strain LP0103.Microbiol Resour Announc. 2022; 11e0040822Crossref PubMed Scopus (1) Google Scholar A total of 13 and 123 contigs were yielded in CMUH-BP250–1 and CMUH-BP250-2, respectively. The prediction of probably antibiotic resistance genes was analyzed by the Comprehensive Antibiotic Resistance Database (CARD) using Resistance Gene Identifier (RGI) software with selection criteria as Perfect and Strict only. The prediction results of both two isolates were identical, which were positive for omp38, amrA, amrB, adeF and blaoxa-59. The mutations in gyrA and amrR were not reported by CARD. The gyrA sequence of B. pseudomallei has not been included in CARD, which has only the gyrA sequence of Burkholderia dolosa. Due to the differences in sequence, GyrA G81D was found only when the Loose hits was added to the selection criteria. The amrR mutation was not included in the CARD. Regarding the present case, the patient had a history of type 2 diabetes mellitus and chronic kidney disease. Diabetes mellitus and chronic renal failure are both main risk factors for melioidosis. Over 50% of patients with melioidosis have diabetes mellitus.2Bzdyl N.M. Moran C.L. Bendo J. Sarkar-Tyson M. Pathogenicity and virulence of Burkholderia pseudomallei.Virulence. 2022; 13: 1945-1965Crossref PubMed Scopus (2) Google Scholar, 3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar Antibiotics remain the backbone of melioidosis treatment, which includes intravenous therapy with ceftazidime or meropenem, followed by oral therapy with trimethoprim-sulfamethoxazole or amoxicillin/clavulanic acid. However, bacteria have developed resistance to a series of antibiotics during treatment.2Bzdyl N.M. Moran C.L. Bendo J. Sarkar-Tyson M. Pathogenicity and virulence of Burkholderia pseudomallei.Virulence. 2022; 13: 1945-1965Crossref PubMed Scopus (2) Google Scholar, 3Wiersinga W.J. Virk H.S. Torres A.G. Currie B.J. Peacock S.J. Dance D.A.B. et al.Melioidosis.Nat Rev Dis Prim. 2018; 4: 17107Crossref PubMed Scopus (313) Google Scholar In this case, levofloxacin was used as the regimen for the confirmed melioidosis due to its in vitro susceptibility against the CMUH-BP250-1 isolate. However, levofloxacin is actually not indicated for the treatment of melioidosis in the eradication and maintenance phases.9Bureros K.J. Chiu Y.C. Liou C.Y. Ma C.Y. Wang L.C. Complete genome sequence of a suckermouth catfish outbreak isolate, Aeromonas hydrophila strain LP0103.Microbiol Resour Announc. 2022; 11e0040822Crossref PubMed Scopus (1) Google Scholar In this study, whether the previous exposure to cefmetazole and levofloxacin might be associated with emergence of meropenem and levofloxacin resistance in CMUH-BP250–2 isolate remained unclear. However, when grown under biofilm-inducing conditions, B. pseudomallei has high potential for developing multiple antibiotic resistance.10Sirijant N. Sermswan R.W. Wongratanacheewin S. Burkholderia pseudomallei resistance to antibiotics in biofilm-induced conditions is related to efflux pumps.J Med Microbiol. 2016; 65: 1296-1306Crossref PubMed Scopus (19) Google Scholar The patient had progressive pneumonia, which may constitute biofilm conditions. In conclusion, use of antibiotics for treating patients with melioidosis should be carefully considered, and more frequent antibiotic susceptibility tests might be needed due to the potential emergence of drug resistance in B. pseudomallei after antibiotic use. This study was approved by the institutional review board of the hospital (CMUH112-REC2-027) and the requirement for informed consent from each patient was waived." @default.
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• W4361248653 title "Emergence of meropenem and levofloxacin resistance in Burkholderia pseudomallei in Taiwan" @default.
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