Search

Background/Purpose Ceftaroline, with a unique activity against methicillin-resistant Staphylococcus aureus (MRSA), was not launched in Taiwan before 2019. The in vitro susceptibility data of ceftaroline against important Taiwanese pathogens are lacking. Methods The in vitro susceptibility of ceftaroline against important pathogens collected from 2012 through 2018 were extracted from the Antimicrobial Testing Leadership and Surveillance program. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) to ceftaroline against all isolates. Results During the study period, the in vitro data regarding isolates of S. aureus (n = 2049), Staphylococcus epidermidis (n = 185), Streptococcus pneumoniae (n = 334), Streptococcus pyogenes (n = 170), Haemophilus influenzae (n = 75), Haemophilus parainfluenzae (n = 10) and Klebsiella pneumoniae (n = 680) regardless of hospital sites of collection were analyzed. Among the S. aureus isolates studied, 19.4% showed MICs of 1 mg/L to ceftaroline, and 4.4% showed in vitro susceptible-dose dependent to ceftaroline (all MICs, 2 mg/L). Most of other Gram-positive cocci, all H. influenzae and H. parainfluenzae isolates were susceptible to ceftaroline. By contrast, about one-third (35.9%) of K. pneumoniae isolates, irrespective of infection sources, exhibited non-susceptibility to ceftaroline (MIC range, 0.015–256 mg/L; MIC50 and MIC90 values, 0.12 and 256 mg/L, respectively). Conclusions From the pharmacodynamic perspectives, the ceftaroline dosage of 600 mg as a 2-h intravenous infusion every 8 h is effective against all S. aureus and other Gram-positive isolates regardless of acquisition sites in Taiwan. Before ceftaroline is prescribed in treatment of the patient with Gram-negative infection, a cautious evaluation about patient's healthcare-associated factor is warranted.

Epidemiological studies have suggested the effects of ambient fine particles (PM2.5) on asthma, but the effects of specific components of PM2.5 on asthma remain to be explored. Here, we studied the effect of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) on asthma acute exacerbation. The data on daily counts of emergency room visits (ERVs) were obtained from Wan Fang Medical Center, Taipei, Taiwan, from 2012 to 2015. The daily concentrations of PM2.5 and pollutant gases were obtained from a local air quality monitoring station. The levels of PM2.5-bound PAH were estimated by an established grid-scale model. Relative risks for ERVs as the increase in the level of ambient pollutants were calculated by using a generalized additive model of Poisson regression. In the present study, we observed statistically significant positive associations between PM2.5 and asthma ERVs for all age groups. PM2.5-bound PAH was also associated with asthma ERVs for all age groups. In the adult subgroup analysis, there was a significant association between PM2.5-bound PAH and asthma ERVs at lags 1 and 2 (RR 1.289, 95% CI 1.050-1.582 and RR 1.242, 95% CI 1.039-1.485). The impacts of air pollution on the risk of pediatric asthma ERV were found to be significant for PM2.5 at lag day 0 (RR 1.310, 95% CI 1.069-1.606). Moreover, pediatric asthma ERVs were significantly associated with the levels of PM2.5-bound PAH at lag 1 and 2 days (RR 1.576, 95% CI 1.371-1.810 and RR 1.426, 95% CI 1.265-1.607). The study provides evidence that PM2.5-bound PAHs were associated with an increased risk of asthma attacks. Our data further suggested that traffic exhaust is a primary source of PM2.5-bound PAHs.

Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.

A total of 74 570 potentially naturally inducible chromosomal AmpC-producing (PNIC-AmpC) Enterobacterales isolates included in the Antimicrobial Testing Leadership and Surveillance Programme were obtained worldwide during 2012-2019 (22 503 from 2012-2014 and 52 067 from 2015-2019). Of these isolates, 117 and 711 obtained during 2012-2014 and 2015-2019, respectively, were carbapenem-resistant Enterobacterales (PNIC-AmpC-CRE). The MICs of ceftazidime-avibactam for these isolates were determined using the broth microdilution method.Genes encoding different Ambler classes of β-lactamases were investigated using multiplex PCR. After 97 isolates harbouring genes encoding metallo-β-lactamases (MβL) were excluded, 731 PNIC-AmpC MβL-negative CRE isolates (101 from 2012-2014 and 630 from 2015-2019) were included in this study.Enterobacter cloacae (E. cloacae) complex species, Escherichia coli (E. coli) and Citrobacter freundii (C. freundii) complex species accounted for 36.3% (n = 265), 30.4% (n = 222) and 11.8% (n = 86), respectively, followed by Providencia species (n = 72), Serratia species (n = 52) and Klebsiella aerogenes (n = 34). The resistance rates to ceftazidime-avibactam for the overall PNIC-AmpC MβL-negative CRE isolates markedly differed between the two periods (35.6% vs. 63.3%; P0.001). Similar trends were observed for the MβL-negative-CR-E. cloacae complex species (47.4% vs. 65.2%; P = 0.046) and MβL-negative-CR-E. coli (16.2% vs. 63.8%; P0.001) but not for MβL-negative-CR-C. freundii complex species (40% vs. 62%; P = 0.153). Amongst the PNIC-AmpC MβL-negative CRE isolates, resistance rates to ceftazidime-avibactam worsened.Caution should be taken when empirically prescribing ceftazidime-avibactam for infections caused by PNIC-AmpC-CRE before susceptibility data are available.

A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.

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 blaContinuous monitoring of susceptibility to clinically important GNB is warranted.

Highlights • Most COVID-19 patients show fever and respiratory symptoms, however they may present extra-respiratory manifestations. • Cardiac, gastrointestinal, hepatic, renal, neurologic, olfactory, gustatory, ocular, cutaneous and haematologic symptoms. • Extra-respiratory symptoms/signs may represent the initial presentation of SARS-CoV-2 infection. • This review is aimed to help clinicians better understand the range of clinical presentations associated with SARS-CoV-2., Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health threat. Although most patients with COVID-19 manifest fever and respiratory tract symptoms, SARS-CoV-2 infection may also involve other organs/systems and present with extra-respiratory manifestations, including cardiac, gastrointestinal, hepatic, renal, neurological, olfactory, gustatory, ocular, cutaneous and haematological symptoms. Occasionally, these extra-respiratory symptoms/signs represent the initial presentation of SARS-CoV-2 infection, prior to fever or respiratory manifestations. Therefore, this comprehensive review of the extra-respiratory manifestations of COVID-19 is intended to help clinicians better understand the range of clinical presentations associated with SARS-CoV-2 infection, allowing the consideration of COVID-19 in differential diagnoses. A screening test for SARS-CoV-2 should be performed when patients have these extra-respiratory manifestations. In addition, clinicians should be alerted to the adverse effects of anti-SARS-CoV-2 agents that can mimic the extra-respiratory manifestations of COVID-19. Moreover, some extra-respiratory manifestations, such as ocular and gastrointestinal involvement, may be caused by direct invasion of SARS-CoV-2. Therefore, protective measures should be taken while managing the associated clinical specimens. Finally, several extra-respiratory manifestations, such as cardiac involvement, acute kidney injury, coagulation disorders and thrombotic complications, could be associated with a poor prognosis.

Introduction The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. Areas covered This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. Expert opinion Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.

Epidemiological studies have suggested the effects of ambient fine particles (PM

An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2–5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.

Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae spp., MDR or extensively drug-resistant (XDR)-Acinetobacter baumannii complex spp., followed by Stenotrophomonas maltophilia, Chryseobacterium indologenes, and Elizabethkingia meningoseptica are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the Klebsiella pneumoniae carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-P. aeruginosa or A. baumannii complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.

Multidrug-resistant (MDR) bacterial infections in humans are increasing worldwide. The global spread of antimicrobial resistance poses a considerable threat to human health. Phage therapy is a promising approach to combat MDR bacteria. An increasing number of reports have been published on phage therapy and the successful application of antibacterials derived using this method. Additionally, the CRISPR-Cas system has been used to develop antimicrobials with bactericidal effects in vivo. The CRISPR-Cas system can be delivered into target bacteria in various ways, with phage-based vectors being reported as an effective method. In this review, we briefly summarise the results of randomised control trials on bacteriophage therapy. Moreover, we integrated mechanisms of the CRISPR-Cas system antimicrobials in a schematic diagram and consolidated the research on phage-delivered CRISPR-Cas system antimicrobials.

Shio-Shin Jean,1,2 Wen-Sen Lee,3,4 Po-Ren Hsueh5,6 on behalf of the SMART Asia-Pacific Group 1Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Departments of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated the prevalence rates of carbapenemase positivity, antibiotic susceptibility, and independent predictors of carbapenemase producers among the Enterobacteriaceae isolates recovered from patients with intra-abdominal infections (IAI) in the Asia-Pacific region between 2008 and 2014.Materials and methods: Multiplex PCR was used for the detection of specific β-lactamases, while the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibiotics among the IAI-related Enterobacteriaceae isolates. We studied the abovementioned parameters in 484 ertapenem-non-susceptible (Erta-NS) isolates and explored the independent predictors of carbapenemase-producing Enterobacteriaceae (CPE) isolates.Results: Eighty (16.5%) Erta-NS-IAI Enterobacteriaceae isolates were found to be CPE. Vietnam and the Philippines had the highest CPE prevalence rates. The IAI isolates of Enterobacter species and Klebsiella pneumoniae followed by Escherichia coli were the three major pathogens with 77.4%, 40.9%, and 11.7% Erta-NS prevalence rates, respectively. Furthermore, the highest CPE prevalence (35%) was noted among the Erta-NS-K. pneumoniae isolates. The CPE isolates harboring the blaNDM, blaKPC, or blaOXA-48-like alleles had higher imipenem MIC levels than those harboring the blaIMP alleles. Using multivariate logistic regression analysis, we concluded that Erta-NS-IAI isolates with an imipenem non-susceptible phenotype (OR, 56.4), with cefepime MIC>8 µg/mL (OR, 4.4), cultured from the peritoneal space samples (tissue or abscess; OR, 3.3), and harboring the extended-spectrum β-lactamase encoding allele (OR, 11.5) are independent predictors of CPE.Conclusion: Imipenem non-susceptibility, cefepime MIC >8 μg/mL, and the peritoneal space as a culture site are independent clinical predictors of CPE among the Erta-NS-IAI Enterobacteriaceae isolates in the Asia-Pacific region. Keywords: intra-abdominal infection, antimicrobial susceptibility, ertapenem-non-susceptible, carbapenemase-producing Enterobacteriaceae

Elizabethkingia meningoseptica, a Gram-negative pathogen once deemed clinically insignificant, tends to cause infections among low-birth-weight infants and immunocompromised patients. Previously, vancomycin was reported to cure several patients with bacteraemia caused by E. meningoseptica. Nevertheless, some laboratory investigations also showed considerable discordance between in vitro vancomycin susceptibility results obtained by the disk diffusion and broth microdilution methods against clinical E. meningoseptica isolates as determined using the criteria for staphylococci recommended by the Clinical and Laboratory Standards Institute (CLSI). In this review, the PubMed database (1960-2017) was searched for studies that reported mainly cases with E. meningoseptica bacteraemia or meningitis treated with vancomycin alone or with regimens that included vancomycin. In addition, the in vitro synergy between vancomycin and other agents against isolates of E. meningoseptica was reviewed. Elizabethkingia meningoseptica bacteraemia appears not to universally respond to intravenous (i.v.) vancomycin-only therapy, especially in patients who require haemodialysis. If i.v. vancomycin is the favoured therapy against E. meningoseptica meningitis, the addition of ciprofloxacin, linezolid or rifampicin might be an option to effectively treat this difficult-to-treat infection. Further clinical studies are needed to determine the clinical efficacy of these combination regimens for the treatment of E. meningoseptica meningitis.

Objectives: To investigate the susceptibility profiles amongst ertapenem-non-susceptible non-carbapenemase-producing Enterobacterales (ETP-NS-non-CPE) isolates. Methods: Minimum inhibitory concentrations (MICs) of 404 ETP-NS-non-CPE isolates collected from different intra-abdominal infection (IAI) sites amongst patients in the Asia-Pacific region during 2008–2014 were determined using the broth microdilution method. The susceptibility results were interpreted according to the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2018. The MICs data of several agents were evaluated based on their published pharmacokinetic/pharmacodynamic (PK/PD) profiles. Results: The majority (>84%) of IAI-ETP-NS-non-CPE isolates – including Escherichia coli (n = 83), Klebsiella pneumoniae (n = 91) and Enterobacter species (n = 210) – were susceptible to imipenem and amikacin. The 193 hepatobiliary ETP-NS-non-CPE isolates exhibited a trend of lower cefepime MIC (≤4 mg/L) distribution than those (n = 145) cultured from the peritoneal space (P = 0.058). Amongst the ETP-NS-non-CP Enterobacter isolates, 65.7% displayed a cefepime MIC ≤ 4 mg/L. In addition, compared with Escherichia coli and Klebsiella pneumoniae isolates, 82.9% and 72.9% of the ETP-NS-non-CP Enterobacter isolates were susceptible to levofloxacin and ciprofloxacin, respectively. Of note, 74.5% and 70.3% of the ETP-NS-non-CP Enterobacter isolates cultured from the hepatobiliary tract and peritoneal space exhibited a ciprofloxacin MIC ≤ 2 mg/L and ≤0.25 mg/L, respectively. Imipenem and amikacin showed good in vitro susceptibility rates against the IAI-ETP-NS-non-CPE isolates. The hepatobiliary ETP-NS-non-CPE displayed lower cefepime MICs than those cultured from the peritoneal space. Additionally, a significant fraction of IAI-ETP-NS-non-CP Enterobacter isolates exhibited ciprofloxacin MIC ≤ 2 mg/L. Conclusion: Based upon the PK/PD analyses, ciprofloxacin, imipenem and cefepime are probably effective against IAI-ETP-NS-non-CPE isolates.

Spread of drug-resistant Gram-negative bacteria (GNB), including carbapenem-resistant (CR)-Pseudomonas aeruginosa, CR-Acinetobacter baumannii, and particularly the third-generation cephalosporin- a...

Data on ceftaroline (CPT) susceptibility amongst clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA, n=1284) and phenotypic non-extended-spectrum β-lactamase-producing (non-ESBL-P) Klebsiella pneumoniae (n=466), obtained from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme from 2012 to 2018, and selected MRSA isolates from patients with bloodstream infections (BSIs) (n=95) from the Surveillance of Multicentre Antimicrobial Resistance in Taiwan (SMART) programme from 2018 to 2019 were analysed. The minimum inhibitory concentrations (MICs) of ATLAS isolates were determined using the broth microdilution method, whereas the MICs of SMART BSI-MRSA isolates were determined using the Etest and MicroScan system. The pharmacokinetic profiles and pharmacodynamic parameters of CPT were applied to explore the optimal dosage against infections caused by Taiwanese MRSA and K. pneumoniae isolates. Approximately 7.1% of ATLAS MRSA isolates were susceptible-dose dependent (S-DD) to CPT, and 19.7% of the non-ESBL-P K. pneumoniae isolates were not susceptible to CPT. Amongst the ATLAS MRSA isolates, the S-DD rates to CPT amongst isolates causing lower respiratory tract infections were 11.9% and 8.5% for isolates from intensive care units (ICUs) and general wards (GWs), and those causing skin and soft tissue infections (SSTIs) were 20% and 5.3% for isolates from ICUs and GWs, respectively (P=0.015). Of the SSTI MRSA isolates from GWs, 22.7% displayed vancomycin MICs >1 mg/L. Amongst 95 SMART BSI MRSA isolates, 28 (46.7%) isolates exhibited lower CPT MICs by the Etest compared with 60 isolates with CPT MICs of 1-2 mg/L by the MicroScan system. CPT 600 mg as a 2-h intravenous infusion every 8 h is suggested for treatment of infections caused by MRSA and phenotypic non-ESBL-P K. pneumoniae in Taiwan.

Shio-Shin Jean,1,2 Min-Chi Lu,3 Zhi-Yuan Shi,4 Shu-Hui Tseng,5 Ting-Shu Wu,6 Po-Liang Lu,7 Pei-Lan Shao,8 Wen-Chien Ko,9 Fu-Der Wang,10,11 Po-Ren Hsueh12,13 1Department of Emergency Medicine and Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan; 4Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Center for Disease Control and Prevention, Ministry of Health and Welfare, Taiwan; 6Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 7Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Pediatrics, Hsin-Chu Branch, National Taiwan University Hospital, Hsin-Chu, Taiwan; 9Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; 10Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 11School of Medicine, National Yang-Ming University, Taipei, Taiwan; 12Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 13Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017. Materials and methods: Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase, imipenemase, OXA-48-like, and mcr-1-5 genes were detected by molecular methods in Enterobacteriaceae isolates. Results: Five (0.7%) E. coli isolates harbored mcr-1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla KPC, bla OXA-48-like, mcr-1, and bla NDM, respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr-1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane–tazobactam (CLZ–TAZ) NS (40.2%, 16.3%, and 71%–80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%–28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime–avibactam (CAZ–AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ–AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ–TAZ than hospital-acquired E. coli isolates. Conclusion: Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella, and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan. Keywords: Enterobacteriaceae, Neisseria gonorrhoeae, extended-spectrum β-lactamases, carbapenemase, ceftolozane–tazobactam, ceftazidime–avibactam

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients’ 30-day mortality. A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients. A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96–142.29; P

Purpose: Extensive multidrug-resistant Acinetobacter baumannii (XDRAB) has increasingly emerged as one of the most difficult bacteria to treat in the healthcare setting. In this study, we intended to evaluate the factors affecting eradicating XDRAB from the respiratory tract, clinical manifestations, and treatment outcomes. Methods: We retrospectively reviewed the medical records of patients who had XDRAB isolated from the respiratory tract in our medical center from January 1, 2012 to February 28, 2013. Results: In total, 87 patients were included in this study. Eradication was achieved in 69 patients (79.3%). The factors that negatively affect eradication of XDRAB by aerosolized colistin therapy for two weeks included: (1) receiving noninvasive mechanical ventilation; (2) being infected/colonized during residency in long-term care facilities; and (3) receiving combination therapy with intravenous tigecycline. The 30-day mortality in patients with versus without eradication was 26.1% versus 55.6%, respectively (p < 0.05), and the in-hospital mortality rate (40.6% vs. 66.7%, p < 0.05), were significantly lower in the eradication group than the noneradication group. Steroid use was associated with significantly higher overall mortality (32% vs. 61%, p < 0.05) in both high and low dose groups. Conclusion: XDRAB eradication from the respiratory tract is associated with improved clinical outcomes. Clinicians should be aware of the possible negative effect of combination therapy with aerosolized colistin and tigecycline for eradicating XDRAB.

In this prospective, observational, multicentre study using data from five countries (Columbia, The Philippines, Portugal, Taiwan and Thailand), the clinical impact of extended-spectrum β-lactamase (ESBL)-producing organisms on hospitalised patients with community-acquired complicated intra-abdominal infections (CA-cIAIs) was compared with that of non-ESBL-producing organisms during the period April 2010 to December 2011. Adult patients (aged ≥18 years) requiring surgery or percutaneous drainage were enrolled and were followed during the first hospitalisation course. An unadjusted statistical comparison of risk factors for ESBL-positive and ESBL-negative patients was performed. Multivariate regression analyses were performed to assess whether length of stay (LOS) in hospital, clinical cure rate and some important clinical characteristics were associated with ESBL positivity. During the study period, a total of 105 adult patients from five countries were enrolled, of whom 17 (16.2%) had CA-cIAI due to ESBL-positive organisms and 88 (83.8%) had CA-cIAI due to ESBL-negative organisms. Escherichia coli was isolated in 73.3% of all samples. Infections were cured in 8 (47.1%) of the patients with CA-cIAI due to ESBL-positive organisms and in 59 (67.0%) of the patients with CA-cIAI due to ESBL-negative organisms (P=0.285). The median LOS was 11.6 days for patients with infections due to ESBL-negative organisms and 17.6 days for patients with infections due to ESBL-positive organisms (P=0.011). Multivariate logistic regression analysis revealed that pre-existing co-morbidities, but not ESBL positivity, were adversely associated with clinical cure of CA-cIAIs. In contrast, duration of hospitalisation was longer for patients with CA-cIAI due to ESBL-positive organisms.