Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-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.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

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.

Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Different epidemiological characteristics between patients with non-hospital-onset and hospital-onset candidemia: a retrospective cohort study.

Candidemia is a life-threatening infectious disease that has varying incidences. Previous studies revealed the differences in clinical characteristics and outcomes between non-hospital-onset (NHO) and hospital-onset (HO) candidemia. This 4-year retrospective research included adult patients with candidemia in a tertiary medical centre in Taiwan, and cases were categorised as NHO and HO candidemia. Survival analysis and risk factors associated with in-hospital mortality were performed using the Kaplan-Meier method and multivariate Cox proportional-hazards models. The analysis included 339 patients, and the overall incidence was 1.50 per 1,000 admission person-year. Of the cases, 82 (24.18%) were NHO candidemia, and 57.52% (195/339) of patients were diagnosed with at least one malignancy. C. albicans was the most commonly isolated species, accounting for 52.21%. Patients with NHO candidemia had a higher proportion of C. glabrata but a lower ratio of C. tropicalis in comparison to the HO group. The all-cause in-hospital mortality rate was 55.75%. Multivariate Cox proportional-hazards models showed that NHO candidemia was a better outcome predictor (adjusted hazard ratio, 0.44). The administration of antifungal therapy within 2 days was a protective factor. In conclusion, NHO candidemia showed distinct microbiological characteristics and a better outcome than HO candidemia.

Antifungal susceptibility of the clinical and environmental strains of Cryptococcus gattii sensu lato in Taiwan.

BACKGROUND: The rare occurrence of human cryptococcosis caused by Cryptococcus gattii sensu lato leads to difficulties in establishing the antifungal susceptibility profile between species of this potentially lethal pathogen, which may be crucial for treating cryptococcosis. OBJECTIVE: To establish an antifungal susceptibility profile of C. gattii s.l. in Taiwan. METHODS: A total of 104 environmental C. gattii s.l. strains (including multilocal sequence typing ST7, ST106, ST274, ST328, ST546, ST548 and ST630) and 21 previously collected clinical strains (including ST7, ST44, ST06, ST274, ST328 and ST329) were included in this study. We determined the minimum inhibitory concentrations (MICs) of six antifungal agents (itraconazole, fluconazole, voriconazole, posaconazole, flucytosine and amphotericin B) against environmental C. gattii s.l. strains and compared the antifungal susceptibility profiles of environmental strains with those of clinical strains. RESULTS: The antifungal susceptibility data demonstrated that the MICs of antifungal agents against environmental strains were comparable to those against clinical strains. Compared with strains of Cryptococcus deuterogattii, those of C. gattii sensu stricto were more susceptible to azoles and flucytosine. The differences in antifungal susceptibility between the strains of each sequence type (ST) were significant. Correlation analysis of MICs revealed cross-resistance between azoles in environmental strains of C. gattii s.l. Geographic differences in the antifungal susceptibility of C. gattii s.l. isolated from different cities in Taiwan were observed in this study. CONCLUSION: Clinical and environmental strains were indistinguishable in antifungal susceptibility. The antifungal susceptibility of C. gattii s.l. is associated with STs. Therefore, establishing an ST-oriented domestic antifungal susceptibility database may help treat C. gattii s.l.-induced cryptococcosis.

Cryptococcus gattii Infection as the Major Clinical Manifestation in Patients with Autoantibodies Against Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.

Molecular epidemiology and phylogenetic analyses of environmental and clinical isolates of Cryptococcus gattii sensu lato in Taiwan.

BACKGROUND: The rare occurrence of cryptococcosis caused by Cryptococcus gattii sensu lato (C. gattii s.l.) leads to the difficulties in studying the molecular epidemiology of this globally emerging disease. OBJECTIVES: To establish the molecular epidemiological profile of C. gattii s.l. in Taiwan, and understand the genetic relationship between locally endemic and global isolates. METHODS: A nationwide survey on environmental C. gattii s.l. in Taiwan was conducted from 2017 to 2019. The geographic distribution and molecular epidemiology based on multilocus sequence typing (MLST) data of the environmental isolates were compared with 18 previously collected clinical isolates. Phylogenetic analysis was performed to elucidate the genetic relationship between the global isolates and the isolates endemic to Taiwan. RESULTS: From a total of 622 environmental samples, 104 (16.7%) were positive for C. gattii s.l.. Seven sequence types were identified among the environmental isolates. The genetic population structure showed that the environmental and clinical isolates were closely linked by sequence types and geographical locations. Phylogenetic analysis revealed the association between the C. gattii s.l. isolates in Taiwan and those from South America and South Asia. The recombination test suggested that, in Taiwan, the C. gattii sensu stricto (C. gattii s.s). isolates undergo clonal reproduction and sexual recombination, whereas C. deuterogattii isolates were clonal. CONCLUSIONS: The molecular epidemiology of environmental C. gattii s.l. isolates is closely linked to the clinical isolates. Phylogenetic analysis of the environmental isolates provides an insight into the mechanisms underlying reproduction and dispersal of C. gattii s.l. in Taiwan.

Association of antihypertensives during hospitalisation with acute respiratory failure in patients with viral pneumonia: A population-based case-control study.

BACKGROUND: We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. METHODS: In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. RESULTS: In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), ß-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. CONCLUSION: Patients with viral pneumonia who received α-blockers, ß-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

The epidemiology, genotypes, antifungal susceptibility of Trichosporon species, and the impact of voriconazole on Trichosporon fungemia patients.

BACKGROUND/PURPOSE: Invasive Trichosporon infections are emerging, but association of different therapeutic management of Trichosporon fungemia and clinical outcomes were rarely reported. This study investigates the epidemiology, species distribution and genotypes of trichosporonosis in Taiwan, and identified the predictors of clinical outcomes in patients with Trichosporon fungemia. METHODS: Strains collected from four medical centers in Taiwan, during 2010-2018. Species identification was confirmed by sequencing of IGS1 region, and antifungal susceptibility was performed using Sensititre YeastOne panel. RESULTS: Among 115 isolates, Trichosporon asahii was the leading species (73.0%), followed by Trichosporon dermatis (11.3%), Trichosporon faecales (6.1%), and Trichosporon montevideense (5.2%). Of the 84 T. asahii isolates, genotype 1 was the predominant (41.7%). High fluconazole minimal inhibitory concentration (MICs,≧8 µg/mL) were observed for 70.2% T. asahii isolates and 16.1% non-asahii Trichosporon isolates. Posaconazole and voriconazole possess the most potent antifungal activity against all Trichosporon isolates, with geometric mean values of 0.251 µg/mL and 0.111 µg/mL, respectively. Fifty-three isolates collected from blood cultures, and 42 patients with fungemia enrolled for the Kaplan-Meier plot which revealed that voriconazole treatment had a significantly better survival rate compared with those without (p = 0.042). In multivariate analysis, source control (odds ratio [OR]: 0.13 95%CI [confidence interval]: 0.02-0.83, p = 0.031) and voriconazole use (OR: 0.11 95%CI: 0.02-0.74, p = 0.023) are independent predictors of 14-day mortality. CONCLUSION: This is the largest series of Trichosporon fungemia up till the present moment. Voriconazole therapy and source control play important roles in 14-day mortality.

High rates of misidentification of uncommon Candida species causing bloodstream infections using conventional phenotypic methods.

BACKGROUND: Candidemia caused by uncommon Candida species is increasing and misidentification may compromise optimal antifungal therapy. This multicenter study aimed to evaluate the accuracy of species-level identification of uncommon Candida. METHODS: Uncommon causative species of candidemia identified in routine laboratories using CHROMagar, API-32C and VITEK-2 Yeast ID system were collected from July 2011 to June 2014. These isolates were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system and sequencing of the internal transcribed spacer and 28S rRNA gene. Susceptibility of the isolates was determined. RESULTS: Of 85 isolates evaluated, Candida guilliermondii (n = 36) was the most common, followed by Candid sake (n = 7) and Candida famata (n = 4). Using DNA-sequencing analysis as standard, none of C. sake and C. famata was correct, while VITEK MS correctly identified 10 of the 11 isolates. With the exclusion of one unspecified Candida by DNA-sequencing methods, the accuracy of conventional methods and VITEK MS was 64.3% and 86.9%, respectively (p = 0.001). Eight isolates were confirmed to be yeasts other than Candida. Compared with other Candida species, C. guilliermondii showed elevated minimal inhibitory concentration of echinocandins. CONCLUSION: Misidentification of uncommon Candida species was common using the conventional methods, especially for C. sake and C. famata. MALDI-TOF MS assisted by DNA-sequencing methods should be considered.

Are we ready for the global emergence of multidrug-resistant Candida auris in Taiwan?

Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.

Disseminated Cryptococcosis Due to Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Absence of Pulmonary Alveolar Proteinosis.

INTRODUCTION: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. METHODS: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. RESULTS: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. CONCLUSIONS: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.

Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection.

Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-γ autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-γ autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 × 10(-6); Pc = 3.08 × 10(-5) and odds ratio 7.16; 95% confidence interval, 3.02-17.05; P = 1 × 10(-7); Pc = 1.4 × 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.

Yeast oropharyngeal colonization in human immunodeficiency virus-infected patients in central taiwan.

A prospective, cross-sectional study was conducted at a medical center in central Taiwan to understand the prevalence, associated factors, and microbiologic features for oropharyngeal yeast colonization in human immunodeficiency virus-infected outpatients. Oral yeast colonization was detected in 127 (45 %) patients, including 21 (16.5 %) colonized by more than one species. Of the 154 isolates, Candida albicans was the most common species (114, 74 %), followed by Candida dubliniensis (10, 6.5 %), Candida glabrata (10, 6.5 %), Candida tropicalis (7, 4.5 %), and 13 others. We found that receiving antituberculous drug (p = 0.046) or atazanavir (p = 0.045) was two predictors for patients colonized by non-C. albicans species (p = 0.005) and risking mixed yeast colonization (p = 0.009). Even though our data showed that clinical antifungal drugs remained effective in vitro against the colonizing yeasts, the increased mixed yeast colonization indicates a potential issue for controlling mixed infections in hospital settings.

Minimum inhibitory concentrations of antifungals against invasive isolates of Cryptococcus species worldwide: Global antifungal antimicrobial testing leadership and surveillance program, 2010-2020.

This study examined the geographic distribution of minimum inhibitory concentrations (MICs) of antifungals against Cryptococcus isolates. Data were collected on the MICs of specific antifungals (amphotericin B, 5-flucytosine, fluconazole, voriconazole, posaconazole, and isavuconazole) against various Cryptococcus species for the period 2010 to 2020 from the Antimicrobial Testing Leadership and Surveillance database. Cryptococcus isolates were collected from samples of blood and cerebrospinal fluid (CSF) from patients hospitalized in different regions worldwide. We applied the epidemiological cutoff values (ECVs) of antifungals against various Cryptococcus species to distinguish wild-type (WT) from non-WT Cryptococcus isolates. A total of 395 isolates of Cryptococcus species cultured from blood (n = 201) or CSF (n = 194) were analyzed. C. grubii (n = 270), C. neoformans (n = 111), and C. gattii (n = 11) were the three predominant species causing bloodstream infections (BSI) or meningitis/meningoencephalitis (MME). The proportion of MICs above the ECV (1 mg/L) for amphotericin B among C. neoformans isolates was significantly lower than that among C. gattii isolates (MICs >0.5 mg/L; P < 0.001), as evaluated using the chi-square test. For most isolates of the three predominant Cryptococcus species, the MICs of new triazoles were ≤0.25 mg/L. The MICs of fluconazole and amphotericin B in the BSI/MME-causing Cryptococcus isolates collected from patients hospitalized in the Asia-Western Pacific region and Europe were significantly lower (i.e., the distributions were more leftward) than those in North America and Latin America. Ongoing monitoring of MIC data for important antifungals against cryptococcosis is crucial.

Hemophagocytic syndrome in A patient of upper urinary tract urothelial cancer after Bacillus Calmette-Guérin instillation: A case report.

Bacillus Calmette-Guérin (BCG) therapy is an adjuvant treatment for urothelial carcinomas of the upper urinary tract (UTUC). BCG therapy can result in various side effects. We present a case of a 67-year-old female with a history of UTUC who developed disseminated tuberculosis following BCG instillation into the upper urinary tract after conservative management. This complex clinical scenario required a multidisciplinary approach, including antibiotic therapy, immunoglobulin infusion, and tailored tuberculosis treatment. The case underscores the importance of vigilance, early detection, and tailored interventions in managing disseminated tuberculosis arising from BCG therapy and rare complications like hemophagocytic syndrome.

Distribution and drug susceptibilities of Candida species causing candidemia from a medical center in central Taiwan.

Invasive fungal infections have increased significantly in the past few decades because of the increase in high-risk populations. To investigate the distribution and drug susceptibilities of such infections, we analyzed all 152 Candida isolates causing candidemia from 2004 to 2006 at the China Medical University Hospital, a medical center in central Taiwan. Candida albicans was the most common species, accounting for 52.6% of the isolates, followed by C. tropicalis (19.7%), C. parapsilosis (14.5%), C. glabrata (8.6%), C. guilliermondii (3.9%), and C. pelliculosa (0.7%). All isolates were susceptible to amphotericin B, anidulafungin, micafungin, and voriconazole according to minimum inhibitory concentrations (MICs) after a 24-h incubation; 0.7%, 6.6%, and 7.9% of isolates were resistant to amphotericin B, fluconazole, and voriconazole, respectively, after 48-h incubation. Both C. albicans and C. parapsilosis had high degrees of agreement for azoles between 24- and 48-h incubation periods, whereas C. glabrata (38.5-46.2%) and C. tropicalis (56.7-63.3%) did not. The majority of the isolates with high azole MICs displayed a trailing growth phenotype. Hence, the MICs of different drugs after 24-h incubation may be considered for prognosis of candidemia.

National surveillance of antimicrobial susceptibilities to ceftaroline, dalbavancin, telavancin, tedizolid, eravacycline, omadacycline, and other comparator antibiotics, and genetic characteristics of bacteremic Staphylococcus aureus isolates in adults: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) program in 2020.

Methicillin-resistant Staphylococcus aureus (MRSA) causes invasive infections and is associated with community-acquired infections (CAIs) and hospital-associated infections (HAIs). In 2020, 315 S. aureus isolates, including 145 methicillin-susceptible S. aureus (MSSA) and 170 MRSA, mainly associated with bacteremia and mostly CAIs, were collected from 16 hospitals in different regions of Taiwan. Minimum inhibitory concentrations (MICs) were determined using the Sensititre™ complete automated AST system. Staphylococcal cassette chromosome mec (SCCmec) types were analysed using multiplex polymerase chain reaction. The median age of patients infected with MRSA was significantly higher than that of patients infected with MSSA (72.5 years vs. 67.0 years, P=0.027). MIC50/MIC90 values of eravacycline and omadacycline were 0.06/0.12, and 0.25/0.5, respectively. Of the MRSA isolates, 4.1% presented susceptible dose-dependence to ceftaroline, most of which (85.7%) were HAI- and Panton-Valentine leukocidin (PVL)-negative. Among the MRSA isolates, 7.1% were not susceptible to telavancin and tedizolid (mainly type IV, PVL-negative, and CAI), 0.6% were not susceptible to daptomycin (type III, PVL-negative, and HAI), and 1.8% were not susceptible to quinupristin/dalfopristin (three isolates were type III, IV, and VT, respectively, and all were PVL-negative), but all were susceptible to dalbavancin. In conclusion, patients with bacteremia caused by MRSA were older than those with bacteremia caused by MSSA, SCCmec type IV was more predominant in CAI than in HAI, and MRSA isolates not susceptible to novel anti-MRSA antimicrobials belonged to types II, III, or IV. Further studies that include comprehensive demographics and more detailed descriptions of other antimicrobial-resistant genes are urgently needed.

Geographic patterns of carbapenem-resistant, multi-drug-resistant and difficult-to-treat Acinetobacter baumannii in the Asia-Pacific region: results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2020.

This study evaluated the in-vitro activity of multiple classes of antibiotics, including novel ß-lactam combination agents, tigecycline and colistin, against carbapenem-resistant (CRAB), multi-drug-resistant (MDRAB) and difficult-to-treat (DTRAB) Acinetobacter baumannii. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Susceptibility profiles and the distribution of selected antimicrobials among countries were illustrated and examined based on the breakpoints of the Clinical and Laboratory Standards Institute, European Committee on Antimicrobial Susceptibility Testing and the US Food and Drug Administration. In total, 847 A. baumannii isolates were evaluated, and 692 isolates were characterized as CRAB, MDRAB or DTRAB. The prevalence of drug-resistant A. baumannii was >70.0% in South Korea, India and China, while the resistance rate of tigecycline was <5.5%. The MICs of meropenem and meropenem/vaborbactam for drug-resistant A. baumannii were equal (both MIC50 and MIC90 were 32 mg/L, range 0.25-32 mg/L). The overall resistance rate remained high for multiple classes of antibiotics, including penicillins, cephalosporins, carbapenems, quinolones and aminoglycosides (>84.0%, >96.0%, >98.0%, >88.0% and >87.0%, respectively), but not colistin or tigecycline (1.1% and 4.3%, respectively). China showed the lowest susceptibility to tigecycline for drug-resistant A. baumannii isolates compared with other countries. In conclusion, the resistance rate of drug-resistant A. baumannii remains high against multiple classes of antimicrobials. Colistin was the most potent agent, followed by tigecycline. The geographic pattern of tigecycline-resistant A. baumannii varied among countries. Therefore, continuous surveillance of A. baumannii resistance profiles in different regions is required.