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Background: Deep neck infections (DNIs) can compromise the airway and are associated with high morbidity and mortality rates. Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia that is associated with several comorbidities. We compared the clinical characteristics of DNI patients with and without DM. Methods: This study recorded the relevant clinical variables of 383 patients with DNIs between November 2016 and September 2022; of those patients, 147 (38.38%) had DM. The clinical factors between DNI patients with and without DM were assessed. Results: Patients with DM were older (p < 0.001), had higher white blood cell counts (p = 0.029) and C-reactive protein levels (CRP, p < 0.001), had a greater number of deep neck spaces (p = 0.002) compared to patients without DM, and had longer hospital stays (p < 0.001). Klebsiella pneumoniae was cultured more frequently from patients with DM than those without DM (p = 0.002). A higher CRP level (OR = 1.0094, 95% CI: 1.0047–1.0142, p < 0.001) was a significant independent risk factor for DM patients with prolonged hospitalization. The lengths of hospital stays in patients with poorly controlled DM were longer than those with well-controlled DM (p = 0.027). Conclusions: DNI disease severity and outcomes were worse in patients with DM than those without DM. Antibiotics effective against Klebsiella pneumoniae should be used for DNI patients with DM. DNI patients with DM and high CRP levels had more prolonged hospitalizations. Appropriate blood glucose control is essential for DNI patients with DM. [ABSTRACT FROM AUTHOR]

Extended-spectrum β-lactamases-producing Escherichia coli , Klebsiella pneumoniae , and Proteus mirabilis (ESBL-producing-EKP) are an increasingly common cause of childhood urinary tract infection (UTI) worldwide. Recognizing the risk factors and antimicrobial resistance patterns may guide new management in this population. This is a retrospective cohort study of over 5 years in Taiwan (2017–2021). Inclusion criteria are hospitalized pediatric patients with the discharge diagnosis of UTI caused by E. coli , Klebsiella pneumoniae , or Proteus mirabilis. ESBL-producing-EKP and non-ESBL-producing-EKP UTI cases were reviewed for characteristics , urinary isolate antibiotics resistance, and clinical outcomes. The incidence rate of ESBL-producing-EKP UTI increased over the study period (Overall incidence rate: 14.1 %, 46/327 patients). Recent antibiotic therapy in ≤6 months (X2 = 11.83, p < 0.01) and a preterm gestational history (X2 = 8.11, p < 0.05) were associated with an increased risk. The proportion of patients with these two risk factors for ESBL acquisition were 37.5 % (X2 = 9.08, p < 0.05). The co-resistance rate of ESBL-producing-EKP to other antimicrobial agents was 63.0 % for gentamicin, 56.5 % for trimethoprim-sulfamethoxazole, 52.2 % for ciprofloxacin, 4.3 % for amikacin, and 2.2 % for imipenem. The generalized linear model analysis identified a significantly longer length of stay (β: 2.85; 95 % confidence interval [CI]: 1.14–4.56; p < 0.01) and intensive care unit duration (β: 5.86; 95 % CI: 1.59–10.12; p < 0.01) among patients with ESBL-producing-EKP UTI. Amikacin should be considered as an alternative antimicrobial choice beyond carbapenems for ESBL-producing-EKP UTI, especially in the context of carbapenem-resistant E. coli/Klebsiella pneumoniae (CRE/CRKP) emergence. [ABSTRACT FROM AUTHOR]

Objective We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. Methods This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. Results CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15–29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45–141.82, P = 0.023). Discussion CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality. [ABSTRACT FROM AUTHOR]

The accelerating prevalence of extended-spectrum β-lactamase (ESBL)-producing and multidrug-resistance (MDR) Escherichia coli (E. coli) become a public health challenge worldwide. This study aimed to discuss the prevalence of drug-resistant E. coli colonization and analyze its risk factors and clinical characteristics among young infants in Southern Taiwan. Stool samples were collected from young infants, aged less than three months, within three days of their hospitalization from September to December 2019 in a tertiary hospital. A questionnaire was designed for parents to complete. E. coli colonies were selected and analyzed for antimicrobial susceptibility. PCR-based multilocus sequence typing was to detect the presence of sequence type ST131 and bla CTX-M genes. Among 100 enrolled infants, 36% had fecal carriage of E. coli isolates, of which twenty nine (80.5%) were MDR, thirteen (36.1%) were ESBL-producing isolates and five (13.8%) and ten (27.7%) were ST131 and strains carrying CTX-M-14 gene, respectively. Compared to non-ST131 and non-CTX-M-14 gene carrier, isolates of ST131 and CTX-M-14 gene carrier showed a significantly higher resistance rate to cefixime, ceftriaxone, and gentamycin, with p value all <0.05. The prevalence of ESBL-producing and MDR E. coli fecal carriage were both high in young infants. The most common sequence type is ST131, of which all are strains carrying CTX-M-14. Further surveillance and investigation to control for the high prevalence of antimicrobial-resistant E. coli fecal carriage among infants in Taiwan are warranted. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae (K. pneumoniae) urinary tract infections pose a significant challenge in Taiwan. The significance of this issue arises because of the growing concerns about the antibiotic resistance of K. pneumoniae. Therefore, this study aimed to uncover potential genomic risk factors in Taiwanese patients with K. pneumoniae urinary tract infections through genome-wide association studies (GWAS). Methods: Genotyping data are obtained from participants with a history of urinary tract infections enrolled at the Tri-Service General Hospital as part of the Taiwan Precision Medicine Initiative (TPMI). A case-control study employing GWAS is designed to detect potential susceptibility single-nucleotide polymorphisms (SNPs) in patients with K. pneumoniae-related urinary tract infections. The associated genes are determined using a genome browser, and their expression profiles are validated via the GTEx database. The GO, Reactome, DisGeNET, and MalaCards databases are also consulted to determine further connections between biological functions, molecular pathways, and associated diseases between these genes. Results: The results identified 11 genetic variants with higher odds ratios compared to controls. These variants are implicated in processes such as adhesion, protein depolymerization, Ca2+-activated potassium channels, SUMOylation, and protein ubiquitination, which could potentially influence the host immune response. Conclusions: This study implies that certain risk variants may be linked to K. pneumoniae infections by affecting diverse molecular functions that can potentially impact host immunity. Additional research and follow-up studies are necessary to elucidate the influence of these risk variants on infectious diseases and develop targeted interventions for mitigating the spread of K. pneumoniae urinary tract infections. [ABSTRACT FROM AUTHOR]

The OXA-48-producing hypervirulent Klebsiella pneumoniae (hvKP) strains were rarely reported. In this study, we characterized three carbapenem-resistant hvKP strains (KP2185, NCRE61, and KP2683-1) isolated from renal abscess, scrotal abscess, and blood samples in a Taiwan hospital. The three strains belonged to two different clones: ST23 K1 (KP2683-1) and ST11 KL64 (KP2185 and NCRE61). KP2683-1 exhibited the highest virulence in an in vivo model. Whole-genome sequencing analysis showed that KP2185 and NCRE61 acquired IncFIB type plasmids containing a set of virulence genes (iroBCDN, iucABCD, rmpA, rmpA2, and iutA), while KP2683-1 acquired an IncL type plasmid harboring blaOXA-48. [ABSTRACT FROM AUTHOR]

This study examined 70 Klebsiella pneumoniae isolates derived from companion animals with urinary tract infections in Taiwan. Overall, 81% (57/70) of the isolates carried extended-spectrum β-lactamase (ESBL) and/or plasmid-encoded AmpC (pAmpC) genes. ESBL genes were detected in 19 samples, with blaCTX-M-1, blaCTX-M-9, and blaSHV being the predominant groups. pAmpC genes were detected in 56 isolates, with blaCIT and blaDHA being the predominant groups. Multilocus sequence typing revealed that sequence types (ST)11, ST15, and ST655 were prevalent. wabG, uge, entB, mrkD, and fimH were identified as primary virulence genes. Two isolates demonstrated a hypermucoviscosity phenotype in the string test. Antimicrobial susceptibility testing exhibited high resistance to β-lactams and fluoroquinolones in ESBL-positive isolates but low resistance to aminoglycosides, sulfonamides, and carbapenems. Isolates carrying pAmpC genes exhibited resistance to penicillin-class β-lactams. These findings provide valuable insights into the role of K. pneumoniae in the context of the concept of One Health. [ABSTRACT FROM AUTHOR]

The identification and antimicrobial susceptibility of Nocardia spp. are essential for guiding antibiotic treatment. We investigated the species distribution and evaluated the antimicrobial susceptibility of Nocardia species collected in southern Taiwan from 2012 to 2020. A total of 77 Nocardia isolates were collected and identified to the species level using multi-locus sequence analysis (MLSA). The susceptibilities to 15 antibiotics for Nocardia isolates were determined by the broth microdilution method, and the MIC50 and MIC90 for each antibiotic against different species were analyzed. N. cyriacigeorgica was the leading isolate, accounting for 32.5% of all Nocardia isolates, and the prevalence of Nocardia isolates decreased in summer. All of the isolates were susceptible to trimethoprim/sulfamethoxazole, amikacin, and linezolid, whereas 90.9% were non-susceptible to cefepime and imipenem. The phylogenic tree by MLSA showed that the similarity between N. beijingensis and N. asiatica was as high as 99%, 73% between N. niigatensis and N. crassostreae, and 86% between N. cerradoensis and N. cyriacigeorgica. While trimethoprim/sulfamethoxazole, amikacin, and linezolid remained fully active against all of the Nocardia isolates tested, 90.9% of the isolates were non-susceptible to cefepime and imipenem. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) inpatients may acquire infections from other pathogens during hospital admission. This is the first research on this subject to be reported from Taiwan. Methods: Confirmed COVID-19 inpatients were enrolled in this study from January 1, 2020 to July 31, 2021. Various types of pathogens in COVID-19 inpatients, with hospital-acquired infections, were identified and analyzed. The clinical characteristics of COVID-19 patients with and without hospital-acquired infections were reviewed and compared. Results: Of the 204 patients included in the study, 32 (15.7%) patients experienced at least one infectious episode. Of 113 recorded episodes of infection, the predominant type was bacterial (88 of 113 infections, 77.9%); the most frequently isolated bacteria were Acinetobacter spp., followed by Stenotrophomonas maltophilia. With regard to viral infections (19 of 113, 16.8%), the Epstein-Barr virus ranked first place among the identified viruses. Four (3.5%) and 2 (1.8%) of 113 infectious episodes were caused by fungi and atypical pathogens. A multivariate analysis revealed that steroid use was an independent factor in hospitalacquired infections (odds ratio [OR], 6.97; 95% confidence interval [CI], 1.15-42.43; p = 0.035). Patients with hospital-acquired infections were associated with increased 28-day and in-hospital mortality (18.8% vs 5.8% and 31.3% and 5.8%; p = 0.023 and <0.01, respectively), and a longer hospital stay (34 vs 19 days; p < 0.001), compared to those without hospital-acquired infections. Conclusion: Our study revealed the unique local epidemiology of hospital-acquired infections among COVID-19 inpatients in Taiwan. These patients were associated with increased mortality and prolonged hospital admissions. [ABSTRACT FROM AUTHOR]

Endogenous endophthalmitis is an uncommon intraocular infection with potentially devastating consequences on vision. Klebsiella pneumoniae is highly prevalent in East Asian countries, with an increasing incidence recently worldwide. This retrospective study investigates infection sources and antibiotic susceptibilities of K. pneumoniae in patients with endogenous K. pneumoniae endophthalmitis (EKE) in Northern Taiwan. One hundred and fifty-seven patients with EKE were reviewed between January 1996 and April 2019. Pyogenic liver abscess (120/157, 76.4%) was the most common infection source, followed by pneumonia (13, 8.3%), urinary tract infection (7, 4.5%), and intravenous drug use (4, 2.5%). Bilateral involvement was identified in 12.1% (19/157) of patients, especially in patients with pyogenic liver abscess (16/120, 13.3%), pneumonia (2/13, 15.4%), and urinary tract infection (1/7, 14.3%). The antibiotic susceptibility rates were 98.1%, 92.5%, 97.5%, 96.8%, 100%, 99.3%, and 100% for amikacin, cefuroxime, ceftazidime, ceftriaxone, carbapenems, ciprofloxacin, and levofloxacin, respectively. Four extended-spectrum β-lactamase-producing multidrug-resistant (MDR) K. pneumoniae isolates were identified. In conclusion, pyogenic liver abscess was the major infection source in EKE. In addition, K. pneumoniae was still highly susceptible to ceftazidime and amikacin, and the MDR K. pneumoniae isolates were not common in EKE. [ABSTRACT FROM AUTHOR]

Background: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied., Objectives: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates., Methods: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed., Results: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes., Conclusion: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes., (© 2024. The Author(s).)

Klebsiella pneumoniae is a common pathogen of nosocomial pneumonia worldwide and community-acquired pneumonia (CAP) in Asia. Previous studies have shown that K. pneumoniae bacteremic CAP is associated with high mortality. We aimed to revisit K. pneumoniae bacteremic pneumonia in the current era and determine the risk factors associated with 28-day mortality. Between January 2014 and August 2020, adult patients with K. pneumoniae bacteremic pneumonia in a medical center in Taiwan were identified. Clinical and microbiological characteristics were compared between CAP and nosocomial pneumonia. Risk factors for 28-day mortality were analyzed using multivariate logistic regression. Among 150 patients with K. pneumoniae bacteremic pneumonia, 52 had CAP and 98 had nosocomial pneumonia. The 28-day mortality was 52% for all patients, 36.5% for CAP, and 60.2% for nosocomial pneumonia. Hypervirulent K. pneumoniae was more prevalent in CAP (61.5%) than in nosocomial pneumonia (16.3%). Carbapenem-resistant K. pneumoniae was more prevalent in nosocomial pneumonia (58.2%) than in CAP (5.8%). Nosocomial pneumonia, a higher Severe Organ Failure Assessment score, and not receiving appropriate definitive therapy were independent risk factors for 28-day mortality. In conclusion, revisiting K. pneumoniae bacteremic pneumonia in the current era showed a high mortality rate. Host factors, disease severity, and timely effective therapy affect the treatment outcomes of these patients. [ABSTRACT FROM AUTHOR]

We conducted a longitudinal epidemiological surveillance of hypervirulent Klebsiella pneumoniae (hvKP) in Taiwan. Bacteremic KP isolates collected from 16 hospitals in Taiwan between 2017 and 2019 were collected, and the virulent serotypes (K1, K2, K20, K54, and K57), antimicrobial susceptibilities, and virulence genes of these isolates were investigated. During the 3-year period, 1,310 bacteremic KP isolates were collected, of which 27.5% belonged to virulent serotypes, including K1 (n = 162), K2 (n = 74), K57 (n = 56), K54 (n = 41), and K20 (n = 27). K1 was the most prevalent capsular serotype, with an annual prevalence of 11–15%, and was equally distributed across the four geographic areas. The prevalence of K2 declined significantly in 2019. According to wzi -K typing results, 87% of K1 isolates were classified as wzi -1. Among K2 isolates, wzi- 72 (55.4%) and wzi -2 (41.9%) were the most common, whereas wzi -206 was the most prevalent (48.2%) among K57 isolates, followed by wzi -77 (25.0%). Wzi -115 accounted for 85.4% of the K54 isolates, whereas wzi -95 accounted for 92.6% of K20 isolates. rmpA was present in 99.4% of K1, 98.6% of K2, 89.3% of K57, 78.0% of K54, and 84.0% of K20 isolates. rmpA2 was present in 100% of K1 and 98.6% of K2 isolates but was only present in 64.3% of K57, 58.5% of K54, and 74.1% of K20 isolates. K1 remains the dominant hvKP serotype and is associated with most virulence genes in Taiwan. Further studies are required to elucidate the significance of other virulent serotypes. [ABSTRACT FROM AUTHOR]

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are of significant clinical concern worldwide. Fosfomycin is one of the limited treatment options for CRKP. However, resistance to fosfomycin in CRKP has been observed. In this study, we aimed to investigate the fosfomycin resistance mechanism of CRKP. Fosfomycin-resistant Klebsiella pneumoniae isolates were collected from four medical centers in Taiwan from 2010 to 2018. The genes that contributed to fosfomycin resistance were amplified and sequenced. Carbohydrate utilization assays and mutagenesis studies were performed to determine the mechanisms underlying fosfomycin resistance. Forty fosfomycin-resistant CRKP strains were collected and used for further analysis. Fourteen strains exhibited low-level resistance (MIC = 256–512 mg/dl), while 26 strains showed high-level resistance (MIC ≥ 1,024 mg/dl). Chromosomal fosAKP I91V was detected in 39/40 fosfomycin-resistant CRKP strains. We observed that amino acid substitution of chromosomal fosAKP I91V increased the MIC of fosfomycin by approximately eight folds, and this was the only mechanism elucidated for low-level fosfomycin resistance. Among the 26 high-level resistance strains, fosAKP I91V combined with transporter deficiencies (18/26, 69.2%) was the most common resistant mechanism, and one strain showed transporter deficiency only. Plasmid-borne fosA3 accounted for 27.0% (7/26) of high-level resistance. Various G3P and G6P transporter gene mutations, including three novel single amino acid mutations (glpT E299D, glpT D274V, and uhpC A393V) were detected in 19 strains. No murA mutation was found in this study. Our study highlights the need for new therapeutic agents for CRKP infections in Taiwan. [ABSTRACT FROM AUTHOR]

Genomic changes in Mycoplasma pneumoniae caused by adaptation to environmental or ecologic pressures are poorly understood. We collected M. pneumoniae from children who had confirmed pneumonia in Taiwan during 2017-2020. We used whole-genome sequencing to compare these isolates with a worldwide collection of current and historical clinical strains for characterizing population structures. A phylogenetic tree for 284 strains showed that all sequenced strains consisted of 5 clades: T1-1 (sequence type [ST]1), T1-2 (mainly ST3), T1-3 (ST17), T2-1 (mainly ST2), and T2-2 (mainly ST14). We identified a putative recombination block containing 6 genes (MPN366‒371). Macrolide resistance involving 23S rRNA mutations was detected for each clade. Clonal expansion of macrolide resistance occurred mostly within subtype 1 strains, of which clade T1-2 showed the highest recombination rate and genome diversity. Functional characterization of recombined regions provided clarification of the biologic role of these recombination events in the evolution of M. pneumoniae. [ABSTRACT FROM AUTHOR]

We set out to study the prevalence of the mcr-1 gene in carbapenemase-producing Klebsiella pneumoniae (CPKP) strains, and to determine whether its presence is associated with a fitness cost. A total of 234 clinical CPKP isolates were collected from a tertiary medical center in Taiwan from January 2018 to January 2019. The mcr-1 and carbapenemase genes were detected by polymerase chain reaction (PCR) followed by Sanger sequencing. The mcr-1 -positive carbapenemase-producing strain was characterized by whole genome sequencing, a plasmid stability test and a conjugation assay. In vitro growth rate and an in vivo virulence test were compared between the parental mcr-1 -positive strain and its mcr-1 plasmid-cured strain. We identified only one mcr-1 positive strain (KP2509), co-harboring bla KPC– 2 and bla OXA– 48, among 234 (1/234, 0.43%) CPKP strains. KP2509 and its Escherichia coli mcr-1 transconjugant showed moderate colistin resistance (MIC = 8 mg/L). The mcr-1 is located on a large conjugative plasmid (317 kb), pKP2509-MCR, with three replicons, IncHI, IncFIB, and IncN. Interestingly, a complete Type IV-A3 CRISPR-Cas system was identified in pKP2509-MCR. Plasmid pKP2509-MCR was highly stable in KP2509 after 270 generation of passage, and the pKP2509-MCR cured strain PC-KP2509 showed similar growth rate and in vivo virulence in comparison to KP2509. The prevalence of mcr-1 in CPKP strains remains low in our center. Notably, we identified a large plasmid with multiple replicons containing both the mcr-1 and the Type IV-3A CRISPR-Cas genes. The further spread of this highly stable plasmid raises concern that it may promote the increase of mcr-1 prevalence in CPKP. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae liver abscess (KPLA) is an emerging syndrome with the initial cases described in Taiwan in the 1980s. There is high mortality with this condition, and immediate aggressive treatment is necessary. Diabetes mellitus (D.M.) is the single most important risk factor for developing KPLA. Here, we describe a rare case of recurrent cryptogenic Klebsiella pneumoniae pyogenic liver abscess (KPLA) in a young man with poorly controlled type 1 D.M. [ABSTRACT FROM AUTHOR]

Background: Reducing the effectiveness of broad-spectrum cephalosporins against Enterobacteriaceae infections has been recognized. This study aimed to investigate risk factors and clinical significance of third-generation cephalosporin nonsusceptibility (3GC-NS) among the cases of monomicrobial Enterobacteriaceae bacteremia (mEB) at regional or district hospitals. Methods: The study was conducted at three hospitals in southern Taiwan between Jan. 2017 and Oct. 2019. Only the first episode of mEB from each adult (aged ≥ 20 years) was included. The primary outcome was in-hospital crude mortality. Results: Overall there were 499 episodes of adults with mEB included, and their mean age was 74.5 years. Female predominated, accounting for 53% of all patients. Escherichia coli (62%) and Klebsiella pneumoniae (21%) were two major causative species. The overall mortality rate was 15% (73/499), and patients infected by 3GC-NS isolates (34%, 172/499) had a higher mortality rate than those by 3GC-susceptible isolates (66%, 327/499) (21% vs 11%, P=0.005). By the multivariate analysis, 3GC-NS was the only independent prognostic determinant (adjusted odds ratio [AOR], 1.78; P=0.04). Of note, male (AOR 2.02, P=0.001), nosocomial-acquired bacteremia (AOR 2.77, P< 0.001), and usage of nasogastric tube (AOR 2.01, P=0.002) were positively associated with 3GC-NS, but P. mirabilis bacteremia (AOR 0.28, P=0.01) and age (AOR 0.98, P=0.04) negatively with 3GC-NS. Conclusion: For adults with Enterobacteriaceae bacteremia, 3GC-NS signifies a significant prognostic impact. Efforts to rapid identification of such antimicrobial resistance profiles should be incorporated into antimicrobial stewardship programs to achieve favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Our objective was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in fluoroquinolone-nonsusceptible Klebsiella pneumoniae (FQNSKP) in Taiwan, 1999-2022., Methods: A total of 938 FQNSKP isolates were identified from 1966 isolates. The presence of PMQR and virulence genes, antimicrobial susceptibility, capsular types, and PMQR-plasmid transferability were determined., Results: An increasing number of PMQR-containing FQNSKP isolates were observed over the study period. Our results showed that 69.0% (647 isolates) of FQNSKP isolates contained at least one PMQR gene, and 40.6%, 37.0%, and 33.9% of FQNSKP carried aac(6')-Ib-cr, qnrB, and qnrS, respectively. None of FQNSKP carried qepA and qnrC. The most common combination of PMQR genes was aac(6')-Ib-cr and qnrB (12.3%). The presence of PMQR genes is strongly related to resistance to aminoglycoside, cephalosporin, tetracycline, and sulfamethoxazole/trimethoprim in FQNSKP. The capsular serotype K64 is the most common serotype we tested in both the non-PMQR and PMQR FQNSKP isolates, while K20 showed a higher prevalence in PMQR isolates. The magA and peg-344 genes showed a significantly higher prevalence rate in non-PMQR isolates than in PMQR isolates. Eleven isolates that carried the PMQR and carbapenemase genes were identified; however, three successful transconjugants showed that the PMQR and carbapenemase genes were not located on the same plasmid., Conclusions: Our results indicated an increasing prevalence of PMQR genes, especially qnrB and qnrS, in FQNSKP in Taiwan. Moreover, the distribution of PMQR genes was associated with capsular serotypes and antimicrobial resistance gene and virulence gene distribution in FQNSKP., Competing Interests: Declaration of Competing Interest The authors report that there are no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance (AMR) is a growing worldwide public health issue due to the overuse and inappropriate use of antibiotics. AMR has been more prevalent during the coronavirus pandemic of 2019 (COVID-19) compared to previous periods. Therefore, this study was conducted to evaluate the AMR profile of common bacteria that were isolated for routine analysis during the pandemic of COVID-19 in Central Taiwan. The main goal of this study was to examine and analyze the AMR patterns both before and after the start of the COVID-19 pandemic., Methods: We conducted a retrospective analysis of clinical samples collected from two different time periods: the 1-year period before the onset of the COVID-19 pandemic (January 2019 to December 2019) and the 2-year period following the start of the pandemic (September 2020 to September 2022). The data for this study were obtained from clinical records, and both bacterial identification and antibiotic susceptibility testing were performed using the Phoenix identification system., Results: Among the 8152 bacterial isolates obtained during the study period from September 2020 to September 2022, 4022 (49.3%) were Escherichia coli, 1346 (16.5%) were Klebsiella pneumoniae, 1156 (14.2%) were Staphylococcus aureus, 887 (10.9%) were Pseudomonas aeruginosa, 376 (4.6%) were Enterococcus faecium, and 365 (4.5%) were Acinetobacter baumannii. The overall prevalence of resistant bacteria during the COVID-19 pandemic was as follows: vancomycin-resistant Enterococcus, 69%; carbapenem-resistant A. baumannii, 65%; methicillin-resistant S. aureus, 49%; carbapenem-resistant K. pneumoniae, 29%; carbapenem-resistant P. aeruginosa, 17%; and carbapenem-resistant E. coli, 2%. Carbapenem-resistant A. baumannii, vancomycin-resistant Enterococcus, carbapenem-resistant K. pneumoniae, and carbapenem-resistant E. coli increased by 19%, 10%, 2%, and 1%, respectively. On the other hand, carbapenem-resistant P. aeruginosa and methicillin-resistant S. aureus decreased by 6%, respectively., Conclusion: This study provides a comprehensive assessment of AMR during the COVID-19 pandemic in Central Taiwan. Understanding the prevalence of AMR is crucial for preventing infection and formulating disease prevention policies. Further research is warranted to elucidate the correlation between AMR and the severity of infection in COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Community onset K. pneumoniae bacteremia (KPB) is a major problem in Taiwan for decades. We aimed to revisit the role of virulent genotype K1/K2 and possible predisposing factors, compared to our published 2007 cohort.Methods: All adult patients with monomicrobial KPB during 2017 at a medical center in Taiwan were prospectively enrolled. We genotyped the major K types of K. pneumoniae strains, and analyzed the role of prior use of antibiotic or proton pump inhibitor (PPI).Results: A total of 213 cases were enrolled. Compared to our previous 2007 study (n = 231), there was a higher percentage of patients with community onset bacteremia (75% vs. 60%, p = 0.003). The overall mortality rate was lower in 2017 (23% vs. 32%, p = 0.02), while the rates of antimicrobial resistance (all classes) were higher in 2017. There were 40 cases of liver abscesses in 2017 (19%), with an overall mortality rate of 7.5%. The prevalence of K1 was similar (16% in 2017 vs. 19% in 2007), but the prevalence of K2 decreased significantly (7% in 2017 vs. 17% in 2007, p = 0.001). After excluding 39 cases without data of recent medication use, 48 of 174 (28%) of patients had received a PPI within 90 days. Patients with recent PPI use had more complicated underlying illnesses, higher antimicrobial resistance, and higher in-hospital mortality, but was negatively associated with liver abscess (4% vs. 24%, p = 0.002). Of patients with community-acquired bacteremia, 51% used antibiotics within 90 days. After excluding 37 patients received antibiotics within 14 days before the detection of bacteremia, patient with antibiotic use within 15-90 days had higher Pittsburgh bacteremia scores (4.5 vs. 2.7, p = 0.04), creatinine levels, and frequency of recent surgery, but was not associated with liver abscess (21% vs. 31%, p = 0.33).Discussion: In summary, after a decade, community onset KPB is still prevalent (1.3 case per 1000 emergency department visit). K1 remains to be the dominant genotype. The association of prior ampicillin/amoxicillin or PPIs use for liver abscess is not confirmed. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes.Patients and Methods: Patients newly diagnosed with type 2 diabetes from 2009 to 2012 were recruited for this population-based and observational study. Diabetes complications severity index (DCSI) score and defined daily dose (DDD) were used for analysis. The multivariable Cox proportional hazards models were used to estimate the risk of KP pneumonia by DPP4i use, with adjustments for propensity score. The Kaplan-Meier method with the log-rank test was used to estimate the risk of KP pneumonia for DPP4i users.Results: 34774 patients were included. The incidence rate of KP pneumonia in DDP4i users was 1.51 per 1000 person-years and that for the comparison was 2.25 per 1000 person-years. DDP4i users also had a significantly lower cumulative incidence of KP pneumonia (log-rank test p-value = 0.03). DDP4i users had a significantly lower risk of developing KP pneumonia compared with nonusers (adjusted HR = 0.67, 95% CI = 0.48-0.95).Conclusions: For public health issue with type2 diabetes and infection, DPP4i use decreased KP pneumonia. Male gender, patients with co-morbidities, patients with higher DSCI score and higher DDD of DPP4i were observed to decrease KP pneumonia infection in our analysis. The possible role of DPP4i causing immunological disturbances should be considered. [ABSTRACT FROM AUTHOR]

Introduction: Klebsiella pneumoniae, a common hospital- and community-acquired pathogen, is notorious for multidrug resistance. This study aimed to better understand the correlation of clinical presentation and microbiological characteristics of the isolates causing bloodstream infections (BSIs) in Taiwan. Methodology: We retrospectively collected 150 isolates derived from K. pneumoniae bacteremia patients in Taiwan in both 2014 and 2016. Clinical data, bacterial serotyping and drug susceptibility tests were comparatively analyzed. Results: Demographic data showed that diabetes mellitus (DM) was the most common underlying disease (44.0%). The overall 30-day mortality rate was 19.3%, and higher mortality was found in patients with malignancy than others (P = 0.023). Serotype distribution was diverse. The major isolates belonged to non-PCR-typeable serotypes (58.7%) associated with hospital-acquired infections (P = 0.007) and in non-DM patients (P < 0.001), while K2 and K20 significantly caused infections and in DM patients (P = 0.046 and P = 0.006, respectively); however, only K2 showed more community-acquired infection (P = 0.022) than other typeable serotypes. Resistance to antibiotics in clinical isolates in the year 2016 was > 24%, including cefazolin (54%), ampicillin-sulbactam (25%) and cefuroxime (25%). Susceptibility to gentamicin, flomoxef, and tigecycline reduced between the two time periods (2014 and 2016). However, the isolates remained highly susceptible to amikacin and ertapenem (> 95%). Conclusions: Patients with cancer had a higher 30-day mortality rate than others. Amikacin and ertapenem are the drugs of choice for the treatment of multidrug-resistant K. pneumoniae BSIs in Taiwan. [ABSTRACT FROM AUTHOR]

Objectives: Emergent antimicrobial-resistant hypervirulent Klebsiella pneumoniae (hvKp) is an important public health issue. We aimed to investigate resistance mechanisms and hypervirulent traits among tigecycline-non-susceptible (TNS) K. pneumoniae clinical strains, focusing on one hvKp strain with in vivo evolution of tigecycline resistance.Methods: TNS K. pneumoniae strains causing invasive diseases in a medical centre in Taiwan between July 2015 and April 2018 were collected. Resistance mechanisms were determined and hvKp strains were defined as rmpA/rmpA2-carrying strains. Isogenic strains with and without tigecycline resistance were subjected to WGS and in vivo virulence testing. Further, site-directed mutagenesis was used to confirm the resistance mechanism.Results: In total, 31 TNS K. pneumoniae strains were isolated, including six hypervirulent strains. Tigecycline resistance mechanisms were mostly caused by overexpression of AcrAB and OqxAB together with up-regulation of RamA or RarA, respectively. One TNS hypervirulent strain (KP1692; MIC=6 mg/L) derived from its tigecycline-susceptible counterpart (KP1677; MIC=0.75 mg/L) showed acrAB overexpression. WGS revealed four genetic variations between KP1677 and KP1692. In addition, using site-directed mutagenesis, we confirmed that a 1 bp insertion in the ramA upstream region (RamR-binding site), leading to ramA and acrAB overexpression in KP1692, was responsible for tigecycline resistance. The in vivo virulence experiment showed that the TNS hvKp strain KP1692 still retained its high virulence compared with KP1677.Conclusions: hvKp strains accounted for 19.4% among TNS strains. We identified alterations in the ramA upstream region as a mechanism of in vivo tigecycline resistance development in an hvKp strain. [ABSTRACT FROM AUTHOR]

Objectives: Epidemic spread of OXA-48-producing Klebsiella pneumoniae, mainly mediated by the transmission of a blaOXA-48-carrying plasmid, has threatened global health during the last decade. Since its introduction to Taiwan in 2013, OXA-48 has become the second most common carbapenemase. We described the transmission and evolution of an OXA-producing K. pneumoniae clone in a single hospital.Methods: Twenty-two OXA-48 K. pneumoniae were isolated between October 2013 and December 2015. Comparative genomic analysis was performed based on the WGS data generated with Illumina and MinION techniques.Results: Seventeen of the 22 OXA-48 K. pneumoniae that belonged to ST11, with the same capsular genotype, KL64, and differed from each other by seven or fewer SNPs, were considered outbreak strains. Eight of the 17 outbreak strains harboured a 65499 bp blaOXA-48-carrying IncL plasmid (called pOXA48). pOXA48 was absent from the remaining nine strains. Instead, a 24.9 kb blaOXA-48-carrying plasmid fragment was integrated into a prophage region of their chromosomes. Transmission routes of the ST11_KL64 K. pneumoniae sublineages, which carried either pOXA48 or chromosomally integrated blaOXA-48, were reconstructed.Conclusions: Clonal expansion of ST11_KL64 sublineages contributed to the nosocomial outbreak of OXA-48 K. pneumoniae. The chromosome-borne blaOXA-48 lineage emerged during a 2 year period in a single hospital. Dissemination of OXA-48, which is vertically transmitted in K. pneumoniae even in the absence of selective pressure from antimicrobials, deserves public health attention. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the clinical characteristics of patients with community-acquired pneumonia (CAP), healthcare-associated pneumonia (HCAP), and hospital-acquired pneumonia (HAP) caused by Klebsiella pneumoniae and analyze the antimicrobial resistance and proportion of hypervirluent strains of the microbial isolates. Methods: We conducted a retrospective study on patients with pneumonia caused by K. pneumoniae at the Taipei Veterans General Hospital in Taiwan between January 2014 and December 2016. To analyze the clinical characteristics of these patients, data was extracted from their medical records. K. pneumoniae strains were subjected to antimicrobial susceptibility testing, capsular genotyping and detection of the rmpA and rmpA2 genes to identify hypervirulent strains. Results: We identified 276 patients with pneumonia caused by K. pneumoniae, of which 68 (24.6%), 74 (26.8%), and 134 (48.6%) presented with CAP, HCAP, and HAP, respectively. The 28-day mortality was highest in the HAP group (39.6%), followed by the HCAP (29.7%) and CAP (27.9%) groups. The HAP group also featured the highest proportion of multi-drug resistant strains (49.3%), followed by the HCAP (36.5%) and CAP groups (10.3%), while the CAP group had the highest proportion of hypervirulent strains (79.4%), followed by the HCAP (55.4%) and HAP groups (41.0%). Conclusion: Pneumonia caused by K. pneumoniae was associated with a high mortality. Importantly, multi-drug resistant strains were also detected in patients with CAP. Hypervirulent strains were prevalent in all 3 groups of pneumonia patients, even in those with HAP. [ABSTRACT FROM AUTHOR]

• First report of bla NDM-1 / bla NDM-4 and bla OXA-181 co-harbouring strains in Taiwan • Discovery of a novel bla NDM-1 + bla OXA-181 hybrid plasmid • An outbreak of bla NDM-4 + bla OXA-181 co-carriage with enhanced carbapenem resistance • The emergence of KL51 carbapenem-resistant Klebsiella pneumoniae The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is related to the transmission of carbapenemase genes. Strains carrying more than one carbapenemase with a broadened spectrum of antibiotic resistance have been detected, which is concerning. Although bla KPC -encoding ST11-KL47/KL64 strains are dominant, other clones are emerging. This study investigated 137 CRKP from patients' blood samples in Taiwan. Polymerase chain reaction (PCR) was used to identify carbapenemase genes and capsular (KL) types. Most strains (56%, 77/137) possessed bla KPC alone; however, 12% (17/137) carried bla NDM + bla OXA-48-like and these strains showed high resistance to imipenem and meropenem. Strains carrying bla NDM + bla OXA-48-like predominantly belonged to KL51 (n =15), followed by KL64 (n =1) and KL47 (n =1). Whole-genome sequencing of one KL51 strain indicated that bla NDM-4 and bla OXA-181 are carried on two different plasmids. PCR was performed using specific primers located in these plasmids, and all bla NDM + bla OXA-48-like -encoding strains except the KL64 strain were considered to carry the two abovementioned plasmids. Genome analysis for the KL64 strain revealed that bla NDM-1 and bla OXA-181 are encoded in one plasmid. Notably, the KL51 bla OXA-181 plasmid shared high sequence similarity with the KL64 bla NDM-1 + bla OXA-181 plasmid, except the KL64 plasmid comprised a 15,040-bp insertion encoding bla NDM-1. The data revealed KL51 as a predominant KL type carrying bla NDM-4 + bla OXA-181 , and identified a novel plasmid carrying bla NDM-1 + bla OXA-181 , highlighting the spread of specific plasmids and clones of CRKP in Taiwan. [ABSTRACT FROM AUTHOR]

Purpose: To examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course., Materials and Methods: The clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score < 8) or a rapid deterioration in consciousness level within 48 h of hospitalization., Results: Among the 127 enrolled patients, 69 had a fulminant clinical course (47 men and 22 women) and 58 did not. The patients with a fulminant clinical course had a significantly higher incidence of end-stage renal disease (ESRD), severe clinical manifestations and higher mortality rate, and the survivors had significantly worse therapeutic outcomes. Klebsiella (K.) pneumoniae (50 strains) was the most important pathogen for the development of a fulminant clinical course, and all strains were susceptible to ceftriaxone and ceftazidime. With treatment, 50.7% (35/69) of the patients with a fulminant clinical course died, and the presence of K. pneumoniae infection was significant prognostic factor., Conclusions: The presence of ESRD, initial presentation of altered consciousness, septic shock, seizures and CSF total protein level and K. pneumoniae infection were significantly associated with a fulminant clinical course of adult CASBM, and patients with this specific infectious syndrome had high mortality and morbidity rates. The presence of K. pneumoniae infection is a significant prognostic factor., (© 2023. The Author(s).)

• Multicentre surveillance of antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. • Increasing carbapenem resistance among clinically important GNB, especially among nosocomial isolates. • bla KPC , especially the bla KPC-2 variant, was detected in 48.4% of carbapenem-resistant Klebsiella pneumoniae isolates. • Low prevalence of the mcr-1 gene. • mcr-1 was detected in different Enterobacteriaceae species, raising concern of potential dissemination. Multicentre surveillance of antimicrobial susceptibility of clinically important Gram-negative bacteria (GNB) from 16 Taiwanese hospitals was performed. Escherichia coli (n = 398), Klebsiella pneumoniae (n = 346), Pseudomonas aeruginosa (n = 252) and Acinetobacter baumannii complex (ABC) (n = 188) bloodstream isolates, non-typhoidal Salmonella (n = 230) and Shigella flexneri (n = 18) from various sources were collected. Antimicrobial MICs were determined using broth microdilution. Genes encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase (VIM), OXA-48-like carbapenemase (OXA-48) as well as mcr-1–5 genes were detected by molecular methods. Rates of carbapenem non-susceptibility were 2.8%, 9.0%, 0.4%, 0%, 10.3% and 48.8% for E. coli, K. pneumoniae, Salmonella, Shigella, P. aeruginosa and ABC, respectively. For carbapenemases, one (0.3%) E. coli harboured bla NDM-1. Fifteen (4.3%), two (0.6%) and two (0.6%) K. pneumoniae contained bla KPC , bla OXA-48 and bla VIM , respectively. Two (0.5%) E. coli and fourteen (4.0%) K. pneumoniae were non-wild-type according to the colistin MIC. Among Enterobacteriaceae with a colistin MIC ≥ 2 mg/L, mcr-1 was detected in one E. coli , two K. pneumoniae and three Salmonella spp. All three mcr-1 -positive Salmonella isolates were collected from community-acquired infections; none of the six mcr-1 -positive Enterobacteriaceae were carbapenem-resistant. Carbapenem resistance has increased among clinically important GNB, especially among hospital-acquired infections. bla KPC , especially the bla KPC-2 variant, was detected in approximately one-half of the carbapenem-resistant K. pneumoniae isolates in this study. Although resistance rates to colistin remained low among Enterobacteriaceae, the finding of mcr-1 from different species raises concern of potential dissemination. [ABSTRACT FROM AUTHOR]

In November 2015, the emergence of a novel plasmid-mediated colistin resistance mechanism was described. So far, there are only two relevant published reports focused solely on Escherichia coli and Salmonella in Taiwan. This paper describes the emergence of colistin-resistant Klebsiella pneumoniae and Enterobacter cloacae clinical isolates harboring mcr-1 on chromosomes in Taiwan. All four mcr-1-positive isolates were from 63 Klebsiella spp., and the isolated Enterobacter spp. were from diseased dogs and cats at Veterinary Teaching Hospital, National Chiayi University. These four isolates were resistant to colistin, amoxicillin, doxycycline and oxytetracycline, and all mcr-1 genes were located on the chromosome, without any flanking ISApl1 or other insertion sequences. The findings suggest that, in addition to food animals and humans, companion animals can serve as reservoirs of mcr-1, adding another layer of complexity to the rapidly evolving epidemiology of plasmid-mediated colistin resistance in the community. Hence we consider it essential to continue to survey resistance to colistin in these bacteria. Continuous microbiological and molecular surveillance is necessary to assist in early detection and minimize the dissemination of mcr-1. [ABSTRACT FROM AUTHOR]

Unlike Escherichia coli, in which the mobile colistin resistance (mcr) genes and their variants have been increasingly detected in isolates from human, animal and environmental samples worldwide, there have been relatively few reports on mcr genes in human Klebsiella pneumoniae. The stability of mcr genes was tested by serial passage of 5 L of K. pneumoniae suspension harbouring mcr genes into 3 mL Luria-Bertani broth without colistin twice daily for 10 days (Supplementary Methods). [Extracted from the article]

Background: Carbapenemase-producing Klebsiella pneumoniae causes high mortality owing to the limited therapeutic options available. Here, we investigated an emergent carbapenem-resistant K. pneumoniae strain with hypervirulence found among KPC-2-producing strains in Taiwan.Methods: KPC-producing K. pneumoniae strains were collected consecutively from clinical specimens at the Taipei Veterans General Hospital between January 2012 and December 2014. Capsular types and the presence of rmpA/rmpA2 were analysed, and PFGE and MLST performed using these strains. The strain positive for rmpA/rmpA2 was tested in an in vivo mouse lethality study to verify its virulence and subjected to WGS to delineate its genomic features.Results: A total of 62 KPC-2-producing K. pneumoniae strains were identified; all of these belonged to ST11 and capsular genotype K47. One strain isolated from a fatal case with intra-abdominal abscess (TVGHCRE225) harboured rmpA and rmpA2 genes. This strain was resistant to tigecycline and colistin, in addition to carbapenems, and did not belong to the major cluster in PFGE. TVGHCRE225 exhibited high in vivo virulence in the mouse lethality experiment. WGS showed that TVGHCRE225 acquired a novel hybrid virulence plasmid harbouring a set of virulence genes (iroBCDN, iucABCD, rmpA and rmpA2, and iutA) compared with the classic ST11 KPC-2-producing strain.Conclusions: We identified an XDR ST11 KPC-2-producing K. pneumoniae strain carrying a hybrid virulent plasmid in Taiwan. Active surveillance focusing on carbapenem-resistant hypervirulent K. pneumoniae strains is necessary, as the threat to human health is imminent. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13-0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01-1.18; P =0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection. [ABSTRACT FROM AUTHOR]

Purpose: To compare the characteristics, visual outcome, and prognostic factors of patients with endogenous endophthalmitis and to determine the association of endophthalmitis with Klebsiella pneumoniae infection.Methods: We retrospectively analyzed records of patients diagnosed with endogenous endophthalmitis from January 2002 to August 2013.Results: A total of 86 patients were diagnosed with endogenous endophthalmitis; 48 patients were infected with K. pneumoniae, 28 patients were infected with other pathogens, and 10 were culture-negative. Diabetes mellitus was more prevalent among patients infected with K. pneumoniae. Liver abscess and urinary tract infection were the leading sources of infection in patients with and without a K. pneumoniae infection, respectively. In patients with endogenous endophthalmitis, poor initial vision (p<0.001) and K. pneumoniae infection (p = 0.048) were significantly associated with a poor visual outcome.Conclusions: Poor initial vision and K. pneumoniae infection were significantly associated with poorer visual outcome for patients with endogenous endophthalmitis. [ABSTRACT FROM AUTHOR]

In this study, we selected bacteremic Klebsiella pneumoniae isolates from the Taiwan Surveillance of Antimicrobial Resistance program. A total of 521 isolates were collected over a period of 2 decades, including 121 from 1998, 197 from 2008, and 203 from 2018. Seroepidemiology showed that the top five capsular polysaccharide types were serotypes K1, K2, K20, K54, and K62, constituting 48.5% of the total isolates, and the respective ratios at each time point have remained similar over the past 2 decades. The antibacterial susceptibility tests showed that K1, K2, K20, and K54 were susceptible to most antibiotics, while K62 was relatively resistant compared to other typeable and nontypeable strains. In addition, six virulence-associated genes, clbA , entB , iroN , rmpA , iutA , and iucA , were predominant in K1 and K2 isolates of K. pneumoniae. In conclusion, serotypes K1, K2, K20, K54, and K62 of K. pneumoniae are the most prevalent serotypes and carry more virulence determinants in bacteremia patients, which may indicate their invasiveness. If further serotype-specific vaccine development is performed, these five serotypes should be included. Since the antibiotic susceptibility profiles were stable over a long duration, empirical treatment may be predicted according to serotype if rapid diagnosis from direct clinical specimens is available, such as PCR or antigen serotyping for serotype K1 and K2. IMPORTANCE This is the first nationwide study to examine the seroepidemiology of Klebsiella pneumoniae using blood culture isolates collected over a period of 20 years. The study found that the prevalence of serotypes remained consistent over the 20-year period, with high-prevalence serotypes associated with invasive types. Nontypeable isolates had fewer virulence determinants than other serotypes. With the exception of serotype K62, the other high-prevalence serotypes were highly susceptible to antibiotics. If rapid diagnosis using direct clinical specimens, such as PCR or antigen serotyping, is available, empirical treatment can be predicted based on serotype, particularly for K1 and K2. The results of this seroepidemiology study could also help the development of future capsule polysaccharide vaccines., Competing Interests: The authors declare no conflict of interest.

Background: New tetracycline derivatives exhibit broad-spectrum antimicrobial activities. This study aimed to assess the in vitro activity of eravacycline against common Enterobacterales., Methods: Clinical Enterobacterales isolates were collected between 2017 and 2021. The minimum inhibitory concentration (MIC) was determined using a broth microdilution test., Results: We identified Klebsiella pneumoniae (n = 300), Escherichia coli (n = 300), Klebsiella oxytoca (n = 100), Enterobacter cloacae complex (n = 100), Citrobacter freundii (n = 100), and Proteus mirabilis (n = 100). All P. mirabilis strains were resistant to eravacycline. Excluding P. mirabilis, the susceptibility rates to eravacycline, omadacycline, and tigecycline were 75.2%, 66.9%, and 73%, respectively. The MIC 50 and MIC 90 (mg/L) of eravacycline were 0.5 and 4 for K. pneumoniae, 0.5 and 1 for E. coli, 0.5 and 1 for K. oxytoca, 0.5 and 2 for E. cloacae complex, and 0.25 and 1 for C. freundii. In cefotaxime non-susceptible and meropenem susceptible Enterobacterales, excluding P. mirabilis, the susceptibility rates of eravacycline, omadacycline, and tigecycline were 69.7%, 57.1%, and 66.2%. We found decreased susceptibility rates of three new tetracycline derivatives against meropenem non-susceptible Enterobacterales (eravacycline: 47.1%, omadacycline: 39.4%, and tigecycline: 39.4%). Eravacycline showed a high susceptibility rate against cefotaxime non-susceptible and meropenem susceptible K. oxytoca (100%), C. freundii (93.2%), E. coli (85.9%), and meropenem non-susceptible E. coli (100%)., Conclusion: This study provides the MIC and susceptibility rate of eravacycline for common Enterobacterales. Eravacycline could be a therapeutic choice for cefotaxime non-susceptible or meropenem non-susceptible Enterobacterales, especially K. oxytoca, C. freundii, and E. coli., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) was up to 30% between 2014 and 2016 in the study hospital. Of these 77 CRKP isolates, 22 isolates with sequence type ST11 carried the new p KPC_P16 plasmid, a p KPC_LK30 variant, and were widely disseminated between 2014 and 2015 in northern Taiwan. [ABSTRACT FROM AUTHOR]

• Clinical characteristics of patients with Klebsiella pneumoniae intestinal colonisation in a general ward upon admission. • Focused on colonisation with hypervirulent and third-generation cephalosporin-resistant (3GCR) K. pneumoniae strains. • In colonising K. pneumoniae strains, 32.2% were 3GCR and 10.3% were hypervirulent. • ESBL and DHA-1 were the predominant resistance mechanisms among the 3GCR strains. • Mortality rates of patients colonised with 3GCR and hypervirulent K. pneumoniae strains were similar. We aimed to investigate the clinical characteristics of patients with hypervirulent and/or third-generation cephalosporin-resistant (3GCR) Klebsiella pneumoniae intestinal colonisation upon admission to a general ward at Taipei Veterans General Hospital in Taiwan in 2017. Stool surveillance cultures were obtained from patients and the clinical characteristics of the patients were studied retrospectively. Klebsiella pneumoniae strains were characterised for antimicrobial susceptibility, mechanisms of the 3GCR phenotype, and the presence of rmpA / A2 genes, which are markers of hypervirulent strains. Whole-genome sequencing was used to identify the relationship between the colonising strain and subsequent infection strain. Of the 408 patients admitted to the general ward, 87 patients with K. pneumoniae intestinal colonisation were identified. Of the 87 colonised patients, 28 (32.2%) and 9 (10.3%) carried 3GCR and hypervirulent K. pneumoniae strains, respectively. Stay in a long-term care facility and diabetes mellitus were more common in patients colonised with 3GCR strains than those with hypervirulent strains. The 28-day mortality rate was similar between the two groups. Major resistance mechanisms among the 3GCR strains involved the presence of extended-spectrum β-lactamase (ESBL) genes (67.9%) and bla DHA-1 (64.3%). One patient colonised with K. pneumoniae developed subsequent bacteraemia caused by the same strain. In conclusion, 3GCR strains were more common than hypervirulent strains in colonised patients, but clinical outcomes were similar. Future studies to elucidate risk factors for intestinal carriage of hypervirulent and 3GCR K. pneumoniae strains are needed for early identification and better management of these patients. [ABSTRACT FROM AUTHOR]

The isolation of OXA-48-producing Enterobacteriaceae has increased dramatically in Mediterranean countries in the past 10 years, and has recently emerged in Asia. Between January 2012 and May 2014, a total of 760 carbapenem non-susceptible Klebsiella pneumoniae (CnSKP) isolates were collected during a Taiwan national surveillance. Carbapenemases were detected in 210 CnSKP isolates (27.6%), including 162 KPC-2 (n = 1), KPC-3, KPC-17, and NDM-1 (n = 1 each), OXA-48 (n = 4), IMP-8 (n = 18), and VIM-1 (n = 24). The four blaOXA-48 CnSKP isolates were detected in late 2013. Herein we report the emergence OXA-48-producing K. pneumoniae isolates in Taiwan. PFGE analysis revealed that the four isolates belonged to three different pulsotypes. Three isolates harboured blaCTX-M genes and belonged to MLST type ST11. In addition, the plasmids belonged to the incompatibility group, IncA/C. One isolate belonged to ST116 and the plasmid incompatibility group was non-typeable. The sequence upstream of the blaOXA-48 gene in all four isolates was identical to pKPOXA-48N1, a blaOXA-48-carrying plasmid. This is the first report of OXA-48-producing Enterobacteriaceae in Taiwan and the second report to identify blaOXA-48 on an IncA/C plasmid in K. pneumoniae. Given that three isolates belong to the same pandemic clone (ST11) and possess the IncA/C plasmid and similar plasmid digestion profile that indicated the role of clonal spread or plasmid for dissemination of blaOXA-48 gene, the emergence of OXA-48-producing K. pneumoniae in Taiwan is of great concern. [ABSTRACT FROM AUTHOR]

The emergence of carbapenemase-producing Klebsiella pneumoniae (CPKP) has become a great concern worldwide. In this study, 994 non-duplicate, carbapenem non-susceptible Klebsiella pneumonia isolates were collected in Taiwan from 2011 to 2013 for detection of the carbapenemase genes, assessment of antimicrobial susceptibility and molecular epidemiology studies. Of these 994 isolates, 183 (18.4%) had carbapenemase genes: 157 (15.8%) KPC (145 KPC-2 and 12 KPC-17), 16 (1.6%) IMP-8, 9 (0.9%) VIM-1, and 1 (0.1%) NDM-1. KPC had the highest prevalence rate among the carbapenemases and represented a major epidemic clone circulating in Taiwan. The ST512 and ST258 KPC-2 KPs were first identified in Taiwan and were grouped into a small cluster in the PFGE profile. In addition, the genetic structure encompassing the blaKPC gene of the ST512 and ST258 isolates showed a different pattern from that of other KPC isolates. ST11 may be a major sequence type circulating in Taiwan, although a specific minor clone has begun to be observed. This is the first report of ST258 and ST512 KPC-2 KP isolates in Taiwan, whether ST258 and ST512 will become the next endemic problems in Taiwan should be closely monitored. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors ( PPIs) increase gastric pH and impair defence mechanisms against ingested pathogens, which may result in the overgrowth of virulent Klebsiella pneumoniae in the intestine and subsequent liver abscess. Aim We investigated the possible association between PPIs use and cryptogenic liver abscess in Taiwan. Methods We conducted a population-based case-control study using data from the National Health Insurance Research Database. A total of 958 adult cases of liver abscess and 3832 age- and sex-matched control patients were enrolled during 2000-2010. Conditional logistic regression was used to estimate the adjusted odds ratios ( ORs) in patients using PPIs before cryptogenic liver abscess. Results The adjusted OR associating current use of PPIs (prescription within the past 30 days) with cryptogenic liver abscess was 4.7 [95% confidence interval ( CI), 2.9-7.8], and recent use of PPIs (prescription within the past 31-90 days) with cryptogenic liver abscess was 2.9 (95% CI, 1.4-6.1). A dose-response relationship was apparent for cumulative dose of PPIs within 90 days. Adjusted OR was highest among the patients receiving PPIs more than 60 cumulative defined daily dose ( OR = 6.5, 95% CI, 2.8-14.9). Conclusion Proton pump inhibitor therapy within the past 90 days was associated with an increased risk of cryptogenic liver abscess. [ABSTRACT FROM AUTHOR]

We first describe two novel variants of blaKPC, blaKPC-16 and blaKPC-17, which were identified in three Klebsiella pneumoniae isolates from a patient in Taiwan. KPC-16 and KPC-17 differed from KPC-2 by two (P202S and F207L) and a single (F207L) amino acid substitutions, respectively. All three isolates with identical pulsotype belonged to sequence type 11. The MICs of the three isolates for colistin and tigecycline were 0.5 μg/mL and 2 μg/mL, respectively. Moreover, an outbreak of at least 39 blaKPC-17- containing K. pneumoniae isolates is ongoing in southern Taiwan in 2014. Physicians should know that blaKPC-17-containing isolates can substantially threaten public health. [ABSTRACT FROM AUTHOR]

Background: Colibactin is a nonribosomal peptide-polyketide synthesized by multi-enzyme complexes encoded by the pks gene cluster. Colibactin-producing Escherichia coli have been demonstrated to induce host DNA damage and promote colorectal cancer (CRC) development. In Taiwan, the occurrence of pyogenic liver abscess (PLA) has been suggested to correlate with an increasing risk of CRC, and Klebsiella pneumoniae is the predominant PLA pathogen in Taiwan Methodology/Principal Findings: At the asn tRNA loci of the newly sequenced K. pneumoniae 1084 genome, we identified a 208-kb genomic island, KPHPI208, of which a module identical to the E. coli pks colibactin gene cluster was recognized. KPHPI208 consists of eight modules, including the colibactin module and the modules predicted to be involved in integration, conjugation, yersiniabactin production, microcin production, and unknown functions. Transient infection of BALB/c normal liver cells with K. pneumoniae 1084 increased the phosphorylation of histone H2AX, indicating the induction of host DNA damage. Colibactin was required for the genotoxicity of K. pneumoniae 1084, as it was diminished by deletion of clbA gene and restored to the wild type level by trans-complementation with a clbA coding plasmid. Besides, BALB/c mice infected with K. pneumoniae 1084 exhibited enhanced DNA damage in the liver parenchymal cells when compared to the isogenic clbA deletion mutant. By PCR detection, the prevalence of pks-positive K. pneumoniae in Taiwan is 25.6%, which is higher than that reported in Europe (3.5%), and is significantly correlated with K1 type, which predominantly accounted for PLA in Taiwan. Conclusions: Our knowledge regarding how bacteria contribute to carcinogenesis has just begun. The identification of genotoxic K. pneumoniae and its genetic components will facilitate future studies to elucidate the molecular basis underlying the link between K. pneumoniae, PLA, and CRC. [ABSTRACT FROM AUTHOR]

Background and aims: Pylephlebitis (septic thrombophlebitis of the portal venous system) is a rare complication of intra-abdominal infection. We aimed to investigate the recent trend of its etiology, clinical manifestation, and prognosis. Methods: We retrospectively studied the etiology, clinical manifestation, and outcome by reviewing the medical records of all imaging-confirmed pylephlebitis cases diagnosed during the period 2002–2011 in a university hospital in Taiwan. To identify the risk factors for pylephlebitis, we randomly selected 160 patients with intra-abdominal infections but without pylephlebitis as the comparison group. Results: We identified 35 cases of pylephlebitis. Most patients were men [29/35 (83 %)]. The median age of the patients was 57 years (range 35–90 years). Unspecified abdominal pain (18/35) and fever (10/35) were the most common clinical manifestations. Klebsiella pneumoniae liver abscess (7/35) and cholangitis (7/35) were the most common etiologies. Liver abscess was a risk factor for pylephlebitis (13/35 vs. 27/160, P = 0.01). With antibiotic therapy, there was no in-hospital mortality, but pylephlebitis was still associated with an excess hospital stay (22.2 ± 17.6 vs. 9.8 ± 7.1 days, P < 0.001). Conclusions: Our study results suggested a different pattern of pylephlebitis from previous Western literature. K. pneumoniae liver abscess (7/35) is an emerging etiology of pylephlebitis in Taiwan. [ABSTRACT FROM AUTHOR]

Susceptibility of isolates of top-ranking Enterobacterales species and Pseudomonas aeruginosa implicated in complicated intra-abdominal infections (cIAI) and urinary tract infections (cUTI) to important antibiotics, including imipenem-relebactam (IMR) and meropenem-vaborbactam (MVB), in Taiwan in 2019 were evaluated. MICs to various antibiotics were determined using broth microdilution method. Susceptibility results were interpreted mainly based on the MIC breakpoints of the Clinical and Laboratory Standards Institute (CLSI) 2021, but susceptibilities of IMR and MVB were interpreted based on the CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2021. Resistance genes amongst carbapenem-non-susceptible (NS) Gram-negative bacteria (GNB) were investigated using multiplex polymerase chain reaction (PCR). Escherichia coli (n = 356), Klebsiella pneumoniae (n = 165) and Enterobacter cloacae complex (n = 42) isolates accounted for 85.3% of the 660 Enterobacterales isolates. The non-susceptibility rates of imipenem (IPM), IMR against isolates of non- Morganellaceae Enterobacterales, and meropenem (MEM), MVB against all Enterobacterales isolates were 92.2%/94.8%, 98.4–98.7%/98.4–99%, 95%/98.2% and 98.8–100%/99.4–100% for the cIAI/cUTI subgroups, respectively. Amongst the 40 IPM-NS-non- Morganellaceae Enterobacterales isolates, when the CLSI 2021 criteria were applied, 10 were NS to IMR, and four Klebsiella pneumoniae isolates (harbouring bla KPC but neither bla MBL nor bla OXA-48 -like genes) were NS to IMR and MVB. Amongst the 93 Pseudomonas aeruginosa isolates under evaluation, the addition of relebactam (4 mg/L) resulted in a 4-to-16-fold reduction in the MICs of IPM in all 15 IPM-NS- Pseudomonas aeruginosa isolates (including 10 porin-deficient ones) not harbouring bla MBL / bla OXA-48 -like genes. Contrastingly, the addition of vaborbactam (8 mg/L) improved the non-susceptibility to MEM in one (20%) of five IPM/MEM-NS Pseudomonas aeruginosa isolates. Continuous monitoring of susceptibility to clinically important GNB is warranted. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae liver abscess syndrome is an emerging disease. Initially was described in the Asiatic southeast, especially in Taiwan, and recently isolated cases have been reported in other countries including Mexico. It is caused by Klebsiella pneumoniae with hipermucoviscosity phenotype associated with K1 phenotype and the presence of rmpA and MagA. We present the case of a 58 years old patient, with diabetes mellitus who developed fever, general malaise and abdominal pain in upper right quadrant. Abdominal computed tomography showed a hipodense image in segment 1 of the liver compatible with liver abscess. In cultures grew Klebsiella pneumoniae with hipermucoviscosity phenotype. The patient responded favorably to the management with drainage of the abscess and antibiotic therapy with ceftriaxone and amykacine. The Klebsiella pneumoniae liver abscess syndrome should be considered in the differential diagnosis protocol of liver abscess. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a well-known Gram-negative pyogenic pathogen that can cause various types of infection. Liver abscesses caused by community-acquired K. pneumoniae infection are commonly reported in Taiwan, especially in people with diabetes mellitus. Meningococcal bacteraemia can present as disseminated pustules and leucocytoclastic vasculitis, but it has rarely been seen in patients with K. pneumoniae infection. To date, there are only two reports in the English literature about K. pneumoniae bacteraemia presenting as generalized pustulosis. We report a third case, occurring in a Taiwanese woman with a community-acquired K. pneumoniae liver abscess leading to sepsis and generalized pustules, complicated by cutaneous leucocytoclastic vasculitis. [ABSTRACT FROM AUTHOR]

Background. Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Use of amoxicillin/ampicillin may lead to overgrowth of K. pneumoniae in the intestine and predispose to KPLA. We used an animal study and nationwide population-based database to investigate the association between ampicillin/amoxicillin use and KPLA in Taiwan.Methods. In an animal study, ampicillin or sterile water was administered orogastrically in serotype K1 K. pneumoniae–colonized mice and the outcome was compared. We identified 855 cases with liver abscess and selected 3420 age- and sex-matched control subjects from the National Health Insurance Research Database. Conditional logistic regression was used to estimate the adjusted odds ratios (ORs) for the association between recent use of ampicillin/amoxicillin and KPLA.Results. Ampicillin administration predisposed K. pneumoniae–colonized mice to increased bacterial burden, liver abscess and necrosis, and lethality. The population-based study showed that the adjusted OR associating the use of ampicillin/amoxicillin within the past 30 days with KPLA was 3.5 (95% confidence interval, 2.5–5.1). No association was found with use in the past 31–90 days.Conclusions. Ampicillin/amoxicillin therapy started within the past 30 days was associated with increased risk for KPLA. We should avoid the overuse of these antibiotics to prevent undesired disease in the endemic area. [ABSTRACT FROM AUTHOR]

Objectives: The global spread and increasing incidence of carbapenem non-susceptible Klebsiella pneumoniae (CnSKP) has made its treatment difficult, increasing the mortality. To establish nationwide data on CnSKP spread and carbapenem-resistance mechanisms, we conducted a national surveillance study in Taiwanese hospitals. Methods: We collected 100 and 247 CnSKP isolates in 2010 and 2012, respectively. The tests performed included antibiotic susceptibility tests; detection of carbapenemase, extended-spectrum β-lactamases (ESBL), and AmpC β-lactamases genes; outer membrane porin profiles; and genetic relationship with pulsed-field gel electrophoresis and multilocus sequence type. Results: The resistance rate of CnSKP isolates to cefazolin, cefotaxime, cefoxitin, ceftazidime, and ciprofloxacin was over 90%. Susceptibility rate to tigecycline and colistin in 2010 was 91.0% and 83.0%, respectively; in 2012, it was 91.9% and 87.9%, respectively. In 2010, carbapenemase genes were detected in only 6.0% of isolates (4 blaIMP-8 and 2 blaVIM-1). In 2012, carbapenemase genes were detected in 22.3% of isolates (41 blaKPC-2, 7 blaVIM-1, 6 blaIMP-8, and 1 blaNDM-1). More than 95% of isolates exhibited either OmpK35 or OmpK36 porin loss or both. Impermeability due to porin mutation coupled with AmpC β-lactamases or ESBLs were major carbapenem-resistance mechanisms. Among 41 KPC-2-producing K. pneumoniae isolates, all were ST11 with 1 major pulsotype. Conclusions: In 2010 and 2012, the major mechanisms of CnSKP in Taiwan were the concomitance of AmpC with OmpK35/36 loss. KPC-2-KP dissemination with the same ST11 were observed in 2012. The emergence and rapid spread of KPC-2-KP is becoming an endemic problem in Taiwan. The identification of NDM-1 K. pneumoniae case is alarming. [ABSTRACT FROM AUTHOR]