Ribotypes and antimicrobial susceptibility profiles of clinical Clostridioides difficile isolates: A multicenter, laboratory-based surveillance in Taiwan, 2019-2021.

BACKGROUND: The clinical burden of Clostridioides difficile infections (CDIs) remains substantial globally. This study aimed to investigate the ribotypes (RTs) and antimicrobial susceptibility of C. difficile isolates collected in Taiwan. METHODS: C. difficile isolates were prospectively collected from four medical centers in Taiwan from 2019 to 2021. In a reference laboratory, in vitro susceptibility to clindamycin, moxifloxacin, metronidazole, vancomycin, fidaxomicin, and rifaximin were tested, and ribotyping was conducted to determine their genetic diversity. RESULTS: A total of 568 C. difficile isolates were included. Metronidazole resistance was not observed, and the susceptibility rate of vancomycin was 99.5 %. Clindamycin showed poor activity against these isolates, with a resistance rate of 74.8 %. Fidaxomicin exhibited potent activity and 97.4 % of isolates were inhibited at 0.25 µg/mL. Rifaximin MIC90 increased from 0.015 µg/mL in 2019 to 0.03 µg/mL in 2020 and 2021. Of 40 RTs identified, two predominant RTs were RT 078/126 (78, 14 %) and 014/020 (76, 13 %). RT 017, traditional harboring truncated tcdA, accounted for 3 % (20 isolates) and there was no isolate belonging to RT 027. The proportions of RT 078 increased from 11.2 % in 2019 to 17.1 % in 2021, and the predominance of RT 078/126 was more evident in central Taiwan. CONCLUSIONS: Vancomycin, fidaxomicin, and metronidazole remain in vitro effective against clinical C. difficile isolates in Taiwan. The reservoirs and genetic relatedness of two major RTs with zoonotic potentials, RT 078/126 and 014/020, warrant further investigations.

Temporal and geographical prevalence of carbapenem-resistant Pseudomonas aeruginosa and the in vitro activity of ceftolozane/tazobactam and comparators in Taiwan-SMART 2012-2021.

OBJECTIVES: To determine the in vitro activities of ceftolozane/tazobactam (C/T) and comparators against Pseudomonas aeruginosa isolates cultured from hospitalised patient samples in Taiwan from 2012 to 2021 with an additional focus on the temporal and geographical prevalence of carbapenem-resistant P. aeruginosa (CRPA). METHODS: P. aeruginosa isolates (n = 3013) were collected annually by clinical laboratories in northern (two medical centres), central (three medical centres), and southern Taiwan (four medical centres) as part of the SMART global surveillance program. MICs were determined by CLSI broth microdilution and interpreted using 2022 CLSI breakpoints. Molecular ß-lactamase gene identification was performed on selected non-susceptible isolate subsets in 2015 and later. RESULTS: Overall, 520 (17.3%) CRPA isolates were identified. The prevalence of CRPA increased from 11.5%-12.3% (2012-2015) to 19.4%-22.8% (2018-2021) (P ≤ 0.0001). Medical centres in northern Taiwan reported the highest percentages of CRPA. C/T, first tested in the SMART program in 2016, was highly active against all P. aeruginosa (97% susceptible), with annual susceptibility rates ranging from 94% (2017) to 99% (2020). Against CRPA, C/T inhibited >90% of isolates each year, with the exception of 2017 (79.4% susceptible). Most CRPA isolates (83%) were molecularly characterised, and only 2.1% (9/433) carried a carbapenemase (most commonly, VIM); all nine carbapenemase-positive isolates were from northern and central Taiwan. CONCLUSION: The prevalence of CRPA increased significantly in Taiwan from 2012 to 2021 and warrants continued monitoring. In 2021, 97% of all P. aeruginosa and 92% of CRPA in Taiwan were C/T susceptible. Routine in vitro susceptibility testing of clinical isolates of P. aeruginosa against C/T, and other newer ß-lactam/ß-lactamase inhibitor combinations, appears prudent.

Treatment outcomes of patients with non-bacteremic pneumonia caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolates: Is there any benefit of adding tigecycline to aerosolized colistimethate sodium?

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 < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27-1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the 14-day patients' outcomes.

Role of vancomycin in the treatment of bacteraemia and meningitis caused by Elizabethkingia meningoseptica.

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.

Bio-Kil, a nano-based disinfectant, reduces environmental bacterial burden and multidrug-resistant organisms in intensive care units.

BACKGROUND/PURPOSE: This prospective before-after study was intended to investigate the effect of Bio-Kil on reducing environmental bacterial burden and healthcare-associated infections (HAIs) in intensive care units (ICUs) at the Municipal Wan-Fang Hospital, Taipei, Taiwan in 2014. METHODS: Four rooms in the medical and surgical ICUs were investigated and designated as study rooms (n = 2) or control rooms (n = 2). Routine disinfection was performed during the pre-intervention period in both room types. Bio-Kil was applied to the fomites and surroundings of the study rooms during the intervention period. Total bacterial burden and proportion of colonization of fomites and surroundings by multidrug-resistance organisms (MDROs) were determined before and after the intervention. The demographic characteristics, underlying conditions, and clinical outcomes of patients were analyzed. RESULTS: After application of Bio-Kil, the bacterial burden declined in both groups, although the reduction was greater in the study rooms as compared with the control rooms (p = 0.001). During the pre-intervention period, 16 patients were admitted to control rooms and 18 patients to study rooms. After the intervention, 22 patients were admitted to control rooms and 21 patients to study rooms. The number of cases of new-onset sepsis declined in the intervention group (from 33% to 23.8%), but increased in the control group (from 25% to 40.9%); however, there was no significant difference in incidence of new-onset sepsis between the study and control rooms after intervention. CONCLUSION: Application of Bio-Kil reduced the environmental bacterial burden and MDROs in ICUs. Further studies are needed to evaluate the efficacy of this nanotechnology-based disinfectant in reducing HAIs.

Comparison of the clinical efficacy between tigecycline plus extended-infusion imipenem and sulbactam plus imipenem against ventilator-associated pneumonia with pneumonic extensively drug-resistant Acinetobacter baumannii bacteremia, and correlation of clinical efficacy with in vitro synergy tests.

BACKGROUND/PURPOSE: To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy. METHODS: The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients. RESULTS: We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality. CONCLUSION: Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Role of aerosolized colistin methanesulfonate therapy for extensively-drug-resistant Acinetobacter baumannii complex pneumonia and airway colonization.

BACKGROUND: Aerosolized colistin methanesulfonate (CMS) has been used for the treatment of extensively drug-resistant Acinetobacter baumannii (XDRAB) pneumonia and eradication of XDRAB colonization in the respiratory tract. The aims of this study were to compare the efficacy, adverse effects, clinical outcomes, and microbiological eradication of the cases of XDRAB pneumonia or colonization. METHODS: We retrospectively reviewed the medical records of patients who received aerosolized CMS for the treatment of pneumonia and airway colonization due to XDRAB. RESULTS: Clinical data from 118 patients were studied. The mean age of 57 patients in the pneumonia group was 79.4 years, and that of 61 patients in the colonization group was 80.0 years. Patients with XDRAB pneumonia were more likely to be ventilator-dependent than colonized patients (46.5% vs. 21.3%; p = 0.005), receive steroid therapy (49.1% vs. 31.1%; p = 0.046), and be admitted to an intensive care unit (ICU) at the time of aerosolized CMS treatment (56.1% vs. 32.8%; p = 0.011). The in-hospital mortality rate was higher in the pneumonia group than the colonization group (50.9% vs. 33.3%; p = 0.05). Microbiological eradication of XDRAB in airway samples was achieved in 75% (89 of 118) patients. In pneumonia patients, XDRAB eradication was associated with resolution or improvement of presenting symptoms and signs of infection by the end of treatment relative to the noneradicated group (57.8% vs. 25%; p = 0.044), but had no influence on 30-day mortality. In colonized patients, no difference in clinical outcomes was noted between the eradicated and noneradicated groups. CONCLUSION: Aerosolized CMS therapy has acceptable efficacy for XDRAB pneumonia, but no proven efficacy for XDRAB airway colonization.

Breakthrough disseminated cryptococcosis during micafungin therapy.

Echinocandins are not active against basidiomycetous yeasts, such as Cryptococcus neoformans, Trichosporon, and Rhodotorula species, and zygomycosis. We present a patient with renal failure and candidemia, who developed a breakthrough fungal infection with cryptococcemia and cryptococcuria while receiving micafungin therapy.