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Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia–Pacific region. Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia–Pacific region.

Background: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0–18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017–2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Background: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). Methods: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. Results: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2–21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. Conclusions: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84–100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69–100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application. Keywords: aminoglycoside, doxycycline, KPC, synergism, tigecycline

Background/purpose: Globally, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen in nosocomial outbreaks. This study aimed to investigate the correlation between the biofilm formation and survival of MDRABs, and to investigate the antiseptic efficacy of hand sanitizers for the MDRABs, embedded with biofilm (MDRAB-Bs). Methods: The MDRABs were selected randomly after pulsed-field gel electrophoresis (PFGE), and their biofilm formation was analyzed. Desiccation and ethanol tolerances were assayed to test the bacterial survival. The antiseptic efficacy of combined chlorhexidine gluconate (CHG) and 70% ethanol agents against MDRAB-Bs were compared with the 70% ethanol cleanser. Results: Eleven MDRABs, which varied in biofilm formation (MRDAB-B) and planktonic type (MDRAB-P), were tested. In desiccation survival, the mean survival time for the MDRAB-Bs was 49.0 days which was significantly higher than that of their planktonic type (17.3 days) (P

Objectives: This study aims to assess the in vitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. Methods: Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a normal inoculum size of 5 × 105 CFU/ml and a high inoculum size of 5 × 107 CFU/ml were measured. Results: Each 33 isolates of extended-spectrum β-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P

Background/purpose: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection. Methods: Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time–kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline. Results: The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06–0.12 μg/mL, 0.03–0.06 μg/mL, and 0.03–0.06 μg/mL, respectively. In time–killing studies, at the concentration of 1 × MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 × MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 × MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 × 105 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14th day. At the inoculum of 1.25 × 106 CFU, the survival rate was 33.3% on the 14th day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test). Conclusion: Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.

Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 Ã 105 CFU/mL by using 1/2à MIC for each alone, and both 1/2à and 1/4à MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2à MIC and 1/4à MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2à MIC and 1/4à MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline