•Increasing carbapenem resistance in Enterobacterales poses a threat to public health.•Several novel agents have been approved for clinical use against carbapenemase-producing Enterobacterales ...(CPE).•Recent advances in identification of CPE have been reviewed.•These include phenotypic, biochemical, immunochromatographic, proteomic and molecular-based methods.
Increasing carbapenem resistance in Enterobacterales poses a threat to public health. In recent decades, this increase in carbapenem resistance has been caused by the global dissemination of carbapenemase-producing Enterobacterales (CPE). Carbapenemases are members of the β-lactamases that are divided into classes A, B and D based on their molecular structures. Although certain traditionally used antibiotics, such as amikacin, polymyxins, tigecycline and fosfomycin, may remain effective against some CPE, their clinical use is limited owing to adverse effects, including renal toxicity, tissue penetration or the requirement for combination treatment. Recently, several novel agents have been approved for clinical use, such as ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, eravacycline, omadacycline, meropenem/vaborbactam, imipenem/cilastatin/relebactam and plazomicin. However, the spectrum of antimicrobial activities and efficacies of novel agents vary depending on the mechanisms associated with carbapenem resistance in Enterobacterales. Therefore, it is of utmost importance to enable accurate and rapid diagnosis of CPE infection, including the determination of their antimicrobial resistance mechanisms. Here, recent advances in methods for the identification of CPE have been reviewed, including phenotypic methods (carbapenemase inactivation methods), biochemical methods Carbapenemase Nordmann-Poirel (Carba NP) test and modified Carba NP test, immunochromatographic methods, proteomic methods matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) and molecular-based methods nucleic acid amplification technologies, hybridisation techniques (microarray) and whole-genome sequencing. Both precise diagnosis and adequate treatment are important to combat the emerging CPE crisis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged ...hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update ...the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.
•C. tropicalis fungaemia caused high mortality (52.0%) in patients with multiple co-morbidities and neutropenia.•Reduced susceptibility to azoles was observed (66.1% susceptibility for fluconazole ...and 43.1% for voriconazole).•Early antifungal treatment may improve outcome, regardless of fluconazole MIC, compared with no treatment within 48 h.
Candida tropicalis is the second most common Candida species causing fungaemia in Taiwan, and decreased susceptibility to fluconazole has been reported. This study analysed the clinical characteristics of adult patients with C. tropicalis fungaemia and the antifungal susceptibilities of isolates at five tertiary hospitals in Taiwan (1 July 2011 to 30 June 2014). A standardised case record form was used retrospectively to collect demographic, clinical and microbiological characteristics, antifungal treatment and outcomes. MICs of non-duplicate isolates were determined using SensititreTM YeastOneTM and were interpreted using cut-off values recommended by the CLSI. A total 248 patients were diagnosed over the study period; 30-day crude mortality was 52.0%. Multivariate analysis showed that high Charlson comorbidity index ≥4 (OR = 2.09, 95% CI 1.22–3.59; P = 0.008), neutropenia (OR = 4.61, 95% CI 1.42–15.00; P = 0.011) and treatment with an azole-based regimen (OR = 0.39, 95% CI 0.17–0.90; P = 0.028) were significantly associated with 30-day mortality. A total of 33.9% of isolates were non-susceptible to fluconazole (MIC50, 2 mg/L; MIC90, 16 mg/L; MIC range, 0.25 to >256 mg/L), whilst 56.9% to voriconazole (MIC50, 0.25 mg/L; MIC90, 1 mg/L; MIC range, 0.015 to >8 mg/L) according to CLSI clinical breakpoints. There was no significant correlation between overall mortality and MICs of fluconazole or voriconazole. This study showed high mortality in patients with C. tropicalis fungaemia, and azole-based antifungal treatment could improve outcomes regardless of fluconazole MICs of infecting isolates compared with patients without any treatment within 48 h.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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.
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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in ...patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients’ nutritional status before the onset of candidemia. A total of 378 patients were enrolled; 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01; 95% CI, 1.24–3.26; p = 0.005), Charlson comorbidity index (HR, 1.10; 95% CI, 1.03–1.18; p = 0.007), Foley catheter use (HR, 1.68; 95% CI, 1.21–1.35; p = 0.002), concomitant bacterial infections (HR, 1.55; 95% CI, 1.11–2.17; p = 0.010), low platelet count (HR, 3.81; 95% CI, 2.45–5.91; p < 0.001), not receiving antifungals initially (HR, 4.73; 95% CI, 3.07–7.29; p < 0.001), and MUST ≥ 2 (HR, 1.54; 95% CI, 1.09–2.17; p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.
Abstract Background/Purpose Recurrent cellulitis is an important clinical issue but the optimal strategy for prophylaxis is not determined. Intramuscular benzathine penicillin at a 4-week interval ...had been adopted in our hospital and the study was conducted to evaluate the efficacy. Methods From January 1, 2009 to May 31, 2013, all patients aged ≥ 18 year, with a history of recurrent cellulitis and having received at least three shots of intramuscular benzathine penicillin for prophylaxis were retrospectively recruited for analysis. Two treatment periods (prophylaxis period and nonprophylaxis period) were defined. The effects of benzathine penicillin prophylaxis and patient characteristics on the incidence rate of recurrent cellulitis were analyzed using Poisson regression model. Results A total of 72 patients were enrolled, including 26 (36.1%) men. The most common underlying conditions were past surgery at the proximal side of the affected limb (38, 52.8%), malignancy (31, 43.1%), and diabetes mellitus (24, 33.3%). The incidence rate of recurrent cellulitis in the prophylaxis period was 0.73 episode/patient-year, significantly lower than that of 1.25 episodes/patient-year in the nonprophylaxis period ( p < 0.001). Tinea pedis was a significant factor associated with increasing incidence of recurrent cellulitis in our cohort. Conclusion Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised its breakpoints for drugs and species because of the increase in non-
infections and their drug resistance. Following global ...trends, the non-
candidemia resistance rate has increased in Taiwan as well. To update the antifungal susceptibility of non-
candidemia isolates, we conducted a multicenter study using the revised break points.
Patients with non-
candidemia infections were identified at five tertiary hospitals in Taiwan from July 1, 2011, to June 30, 2014. The broth microdilution method using a Sensititre YeastOne system was performed for the determination of minimum inhibitory concentration (MIC). The susceptibility was interpreted based on the guidelines of the CLSI (CLSI M27-S4 and M27-S3).
was the predominant non-
candidemia pathogen (42.4%), and it showed increased fluconazole non-susceptibility (36.3%) when compared to the results from previous studies. In particular,
showed high cross-resistance to azole agents.
isolates that were found to be resistant to fluconazole also showed increased resistance to voriconazole (82.2%) and posaconazole (100%). The increased non-susceptibility of
to multiple antifungal agents, based on the revised break points, resulted from an increase in dose-dependent susceptibility (94.4%) rather than from an increase in resistance (5.6%).
The resistance rate of non-
candidemia isolates is increasing, particularly for
and
.
Background Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods Clinical and laboratory data from ...patients with candidemia were collected retrospectively at a tertiary medical center in Taiwan from July 1, 2009 to June 30, 2012 (a 36-month period). Demographics, clinical characteristics, and drug susceptibility of the invading Candida species of patients at the onset of candidemia were analyzed and compared with previous study from January 1, 2001 to June 30, 2003 (a 30-month period). Results A total of 209 episodes of candidemia in 205 patients were identified in this study period. When compared with the previous study period, more patients were admitted for medical conditions at percentages ranging from 49.5% to 69.8%; the incidence rate of health care-associated candidemia increased from 0.76 to 1.14 per 1000 discharges; the proportion of Candida albicans in patients with candidemia decreased from 64.8% to 43.6% whereas the proportion of Candida glabrata increased greatly from 1.1% to 21.6% and the proportions of Candida tropicalis and Candida parapsilosis were slightly elevated (19.8–22.0% and 2.2–7.3%, respectively). All of the C. albicans isolates remained susceptible to fluconazole, whereas 66.7% of C. glabrata isolates were dose-dependent susceptible, and 4.4% of C. glabrata isolates and 11.6% C. tropicalis isolates were resistant. There was one C. glabrata and one Candida guilliermondii resistant to echinocandin. The predictors for 30-day mortality included the high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, use of parenteral nutrition, underlying malignancy, liver cirrhosis, and neutropenia whereas candidemia by C. parapsilosis or C. glabrata is a favorable predictor when compared with C. albicans. Conclusion The distribution of Candida species in candidemia was changed. Although C. albicans remained the major species, the isolation of non- C. albicans spp., especially C. glabrata, increased. Patients with candidemia still had high mortalities due to severity of illness and underlying conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing antiretroviral therapy (ART) in management of latent tuberculous ...infection (LTBI) is limited among people with human immunodeficiency virus (PWH).
From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment; secondary outcomes included treatment completion rate and safety of LTBI regimens.
During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate.
Combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.
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