Transformation from zero tolerance to living with COVID-19 in New Taipei City, Taiwan. Experience of the FEMH "home-hotel-hospital" care model.

In March 2022, local cases of COVID-19 infections of the Omicron variant were identified in Taiwan. In response to impending community transmission, the "Home-Hotel-Hospital" (3H) care model was implemented by the Far Eastern Memorial Hospital (FEMH). It established the first remote home care center in Taiwan and two quarantine centers in two hotels. The hospital focused on care for critical COVID-19 patients, community screening, and telehealth care. The home care call center evaluated and triaged up to 104,244 cases and provided remote home care for 96,894 cases within the first three months; in 2022, it provided home care to 107,095 patients. The two quarantine hotels admitted a total of 1834 individuals. A total of 3796 COVID-19 patients were admitted to the hospital-367 in intensive care. The telehealth outpatient clinic-including the online video clinic-served 25,775 cases; 21.5% (n = 5544) of them were prescribed oral anti-viral medications. In 2022, the FEMH prescribed oral anti-viral therapies to a total of 12,571 cases. The FEMH 3H care model not only enabled non-critical patients to recover at home, but also provided severely ill patients access to timely in-hospital care. In the future, this model will continue to play a significant role in COVID-19 management.

Preventing and controlling intra-hospital spread of COVID-19 in Taiwan - Looking back and moving forward.

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.

Role of yceA-cybB-yceB operon in oxidative stress tolerance, swimming motility and antibiotic susceptibility of Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia is ubiquitous in the environment and is an important MDR opportunistic pathogen. Oxidative stress is an inevitable challenge to an aerobic bacterium. Accordingly, S. maltophilia has many capabilities to face variable oxidative stress. Some of the oxidative stress alleviation systems cross-protect bacteria from antibiotics. In our recent RNA-sequencing transcriptome analysis, we documented the increased expression of a three-gene cluster, yceA-cybB-yceB, in the presence of hydrogen peroxide (H2O2). The YceI-like, cytochrome b561 and YceI-like proteins encoded by yceA, cybB and yceB are located in the cytoplasm, inner membrane and periplasm, respectively. OBJECTIVES: To characterize the role of the yceA-cybB-yceB operon of S. maltophilia in oxidative stress tolerance, swimming motility and antibiotic susceptibility. METHODS: The presence of the yceA-cybB-yceB operon was verified by RT-PCR. The functions of this operon were revealed by in-frame deletion mutant construction and complementation assay. Expression of the yceA-cybB-yceB operon was assessed by quantitative RT-PCR. RESULTS: The yceA, cybB and yceB genes form an operon. Loss of function of the yceA-cybB-yceB operon compromised menadione tolerance, enhanced swimming motility and increased susceptibility to fluoroquinolone and ß-lactam antibiotics. The expression of the yceA-cybB-yceB operon was up-regulated by oxidative stress, such as H2O2 and superoxide, and not impacted by antibiotics, such as fluoroquinolone and ß-lactams. CONCLUSIONS: The evidence strongly supports the view that the physiological function of the yceA-cybB-yceB operon is to alleviate oxidative stress. The operon provides an additional example that oxidative stress alleviation systems can cross-protect S. maltophilia from antibiotics.

The fciTABC and feoABI systems contribute to ferric citrate acquisition in Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia, a member of γ-proteobacteria, is a ubiquitous environmental bacterium that is recognized as an opportunistic nosocomial pathogen. FecABCD system contributes to ferric citrate acquisition in Escherichia coli. FeoABC system, consisting of an inner membrane transporter (FeoB) and two cytoplasmic proteins (FeoA and FeoC), is a well-known ferrous iron transporter system in γ-proteobacteria. As revealed by the sequenced genome, S. maltophilia appears to be equipped with several iron acquisition systems; however, the understanding of these systems is limited. In this study, we aimed to elucidate the ferric citrate acquisition system of S. maltophilia. METHODS: Candidate genes searching and function validation are the strategy for elucidating the genes involved in ferric citrate acquisition. The candidate genes responsible for ferric citrate acquisition were firstly selected using FecABCD of E. coli as a reference, and then revealed by transcriptome analysis of S. maltophilia KJ with and without 2,2'-dipyridyl (DIP) treatment. Function validation was carried out by deletion mutant construction and ferric citrate utilization assay. The bacterial adenylate cyclase two-hybrid system was used to verify intra-membrane protein-protein interaction. RESULTS: Smlt2858 and Smlt2356, the homologues of FecA and FecC/D of E. coli, were first considered; however, deletion mutant construction and functional validation ruled out their involvement in ferric citrate acquisition. FciA (Smlt1148), revealed by its upregulation in DIP-treated KJ cells, was the outer membrane receptor for ferric citrate uptake. The fciA gene is a member of the fciTABC operon, in which fciT, fciA, and fciC participated in ferric citrate acquisition. Uniquely, the Feo system of S. maltophilia is composed of a cytoplasmic protein FeoA, an inner membrane transporter FeoB, and a predicted inner membrane protein FeoI. The intra-membrane protein-protein interaction between FeoB and FeoI may extend the substrate profile of FeoB to ferric citrate. FeoABI system functioned as an inner membrane transporter of ferric citrate. CONCLUSIONS: The FciTABC and FeoABI systems contribute to ferric citrate acquisition in S. maltophilia.

Novel design of amine and metal hydroxide functional group modified onto sludge biochar for arsenic removal.

This study involved novel-designed sludge biochar (SB) adsorbed for arsenic removal with lower operating costs and higher adsorption efficiency properties. Generally, biochar only relies on micropores for pollutant adsorption, but physical adsorption is not highly efficient for arsenic removal. Therefore, in order to improve the removal efficiency of arsenic by SB, diethylenetriamine (DETA) and FeCl3 were used in this study to modify the surface of SB by an immersion method. The objectives of this research are to obtain optimum operation conditions by assessing the effect of different Fe content, pH and initial concentration on adsorbing arsenic. This study is the first to use Density Functional Theory (DFT) to simulate and verify the adsorption mechanism of arsenic by SB. Results showed the presence of amine/iron oxyhydroxides functional groups greatly promoted SB surface activity and its arsenic adsorption potential. The surface area, pore volume and pore size of the SB were estimated to be 525 m2 g-1, 0.35 cm3 g-1 and 8.71 nm, respectively. The DFT model result is the same as the result of arsenic adsorption performance with high adsorption energy (-246.3 kJmol-1) and shorter bond distances (1.42 Å), indicating strong chemical adsorption between arsenic and material. The reaction mechanism is divided into four pathways, including oxidation-reduction, complexation, electrostatic adsorption and pore adsorption.

Impact of Immunosuppressive Agents on Clinical Manifestations and Outcome of Staphylococcus aureus Bloodstream Infection: A Propensity Score-Matched Analysis in 2 Large, Prospectively Evaluated Cohorts.

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations.

AmpR of Stenotrophomonas maltophilia is involved in stenobactin synthesis and enhanced ß-lactam resistance in an iron-depleted condition.

BACKGROUND: Iron is an essential nutrient for almost all aerobic organisms, including Stenotrophomonas maltophilia. Fur is the only known transcriptional regulator presumptively involved in iron homeostasis in S. maltophilia. AmpR, a LysR-type transcriptional regulator, is known to regulate ß-lactamase expression and ß-lactam resistance in S. maltophilia. OBJECTIVES: To identify the novel regulator involved in controlling the viability of S. maltophilia in an iron-depleted condition and to elucidate the underlying regulatory mechanisms. METHODS: The potential regulator involved in iron homeostasis was identified by studying the cell viabilities of different regulator mutants in 2,2'-dipyridyl (DIP)-containing medium. Iron-chelating activity was investigated using the chrome azurol S (CAS) activity assay. An iron source utilization bioassay was carried out to examine utilization of different iron sources. Gene expression was determined by quantitative real-time PCR, and the Etest method was used to evaluate antibiotic susceptibility. RESULTS: Of the 14 tested mutants, the ampR mutant, KJΔAmpR, showed a growth compromise in DIP-containing medium. AmpR regulated stenobactin synthesis in an iron-depleted condition, but showed little involvement in the uptake and utilization of ferri-stenobactin and ferric citrate. AmpR was up-regulated by iron limitation and ß-lactam challenge. S. maltophilia clinical isolates grown under conditions of iron depletion were generally more resistant to ß-lactams compared with conditions of iron repletion. CONCLUSIONS: AmpR is a dual transcriptional regulator in S. maltophilia, which regulates the ß-lactam-induced ß-lactamase expression and iron depletion-mediated stenobactin synthesis. AmpR is, therefore, a promising target for the development of inhibitors.

Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018.

A total of 598 Neisseria gonorrhoeae isolates obtained from patients in Taiwan from 2001 to 2018 were evaluated. The MICs of ceftriaxone (CRO) and azithromycin (AZM) against the isolates were determined by the agar dilution method. N. gonorrhoeae isolates with AZM MICs of ≥1 µg/ml were identified and characterized by the presence of AZM resistance determinants. For high-level AZM-resistant (AZM-HLR) isolates (MIC ≥ 256 µg/ml), genotyping was performed using multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Among the N. gonorrhoeae isolates studied, 8.7% (52/598) exhibited AZM MICs of ≥1 µg/ml. Thirteen of the 52 isolates contained A2059G (23S rRNA NG-STAR type 1) or C2611T (23S rRNA NG-STAR type 2) mutations. The prevalence of the A2059G mutation was higher in AZM-HLR isolates (P < 0.001). The -35A deletion in the promoter region of the mtrR gene did not differ between AZM-HLR isolates (100%, 10/10) and the isolates with AZM MICs of 1 µg/ml to 64 µg/ml (95.2%, 40/42) (P = 1.000). The presence of mutations in the mtrR coding region was significantly different between these two groups at 90% (9/10) and 26.2% (11/42), respectively (P < 0.001). The AZM-HLR isolates, all carrying four mutated A2059G alleles, a -35A deletion, and G45D, were classified as MLST 12039/10899 and NG-MAST 1866/16497. In conclusion, Taiwan is among the countries reporting gonococci with high-level resistance to AZM so that a single dose of 1 g ceftriaxone intramuscularly as the first choice for management of N. gonorrhoeae infection should be evaluated.

In vitro activities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and Stenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan.

Objectives: We investigated the in vitro activities of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam and other related drugs against imipenem-resistant Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumannii and Stenotrophomonas maltophilia isolates. Methods: Non-duplicated bacteraemia isolates (n = 300) of imipenem-resistant P. aeruginosa (n = 100), imipenem-resistant A. baumannii (n = 100) and S. maltophilia (n = 100) were evaluated. Imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii isolates were defined as isolates exhibiting imipenem MIC ≥8 mg/L, as determined using the VITEK 2 system. The MICs of 11 other antimicrobial agents for the isolates were determined by the broth microdilution method. Iron-depleted CAMHB was used to determine the MICs of cefiderocol. Results: The rates of colistin resistance of imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii were 5% and 10%, respectively. The MIC90 values of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam, tigecycline and colistin were as follows: imipenem-resistant P. aeruginosa: 1, 4, 16, >4 and 2 mg/L; imipenem-resistant A. baumannii: 8, >64, >64, 4 and 2 mg/L; and S. maltophilia: 0.25, >64, >64, 2 and >8 mg/L, respectively. For imipenem-resistant A. baumannii isolates, the MICs of cefiderocol, ceftolozane/tazobactam and ceftazidime/avibactam were ≤4 mg/L for 88%, 8% and 1% of the isolates, respectively. Cefiderocol MICs were ≤4 mg/L for the five colistin-resistant imipenem-resistant P. aeruginosa isolates and 70% of the 10 colistin-resistant imipenem-resistant A. baumannii isolates. Conclusions: Cefiderocol exhibited more potent in vitro activity than ceftolozane/tazobactam and ceftazidime/avibactam against imipenem-resistant P. aeruginosa, imipenem-resistant A. baumannii and S. maltophilia isolates.

Effective disinfection of airborne microbial contamination in hospital wards using a zero-valent nano-silver/TiO2 -chitosan composite.

A novel antimicrobial composite of zero-valent silver nanoparticles (AgNPs), titania (TiO2 ), and chitosan (CS) was prepared via photochemical deposition of AgNPs on a CS-TiO2 matrix (AgNPs@CS-TiO2 ). Electron microscopy showed that the AgNPs were well dispersed on the CS-TiO2 , with diameters of 6.69-8.84 nm. X-ray photoelectron spectra indicated that most of the AgNPs were reduced to metallic Ag. Fourier-transform infrared spectroscopy indicated that some AgNPs formed a chelate with CS through coordination of Ag+ with the CS amide II groups. The zones of inhibition of AgNPs@CS-TiO2 for bacteria (Escherichia coli and Staphylococcus epidermidis) and fungi (Aspergillus niger and Penicillium spinulosum) were 6.72-11.08 and 5.45-5.77 mm, respectively, and the minimum (critical) concentrations of AgNPs required to inhibit the growth of bacteria and fungi were 7.57 and 16.51 µg-Ag/mm2 , respectively. The removal efficiency of a AgNPs@TiO2 -CS bed filter for bioaerosols (η) increased with the packing depth, and the optimal filter quality (qF) occurred for packing depths of 2-4 cm (qF = 0.0285-0.103 Pa-1 ; η = 57.6%-98.2%). When AgNPs@TiO2 -CS bed filters were installed in the ventilation systems of hospital wards, up to 88% of bacteria and 97% of fungi were removed within 30 minutes. Consequently, AgNPs@TiO2 -CS has promising potentials in bioaerosol purification.

Genes and Proteins Involved in qnrS1 Induction.

Expression of the quinolone resistance gene qnrS1 is increased by quinolones, but unlike induction of some other qnr genes, the bacterial SOS system is not involved and no lexA box is found upstream. Nonetheless, at least 205 bp of upstream sequence is required for induction to take place. An upstream sequence bound to beads trapped potential binding proteins from cell extracts that were identified by mass spectrometry as Dps, Fis, Ihf, Lrp, CysB, and YjhU. To further elucidate their role, a reporter plasmid linking the qnrS1 upstream sequence to lacZ was introduced into cells of the Keio collection with single-gene deletions and screened for lacZ expression. Mutants in ihfA and ihfB had decreased lacZ induction, while induction in a cysB mutant was increased and dps, fis, lrp, yjhU, and other mutants showed no change. The essential upstream sequence contains potential binding sites for Ihf and DnaA. A dnaA deletion could not be tested because it provides essential functions in cell replication; however, increased dnaA expression decreased qnrS1 induction while decreased dnaA expression enhanced it, implying a role for DnaA as a repressor. In a mobility shift assay, purified IhfA, IhfB, and DnaA proteins (but not CysB) were shown to bind to the upstream segment. Induction decreased in a gyrA quinolone-resistant mutant, indicating that GyrA also has a role. Thus, quinolones acting through proteins DnaA, GyrA, IhfA, and IhfB regulate expression of qnrS1.

Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects.

OBJECTIVE: Several studies suggested that colonic microbiota have impacts on irritable bowel syndrome (IBS) patients. However, the knowledge about the association of small intestine (SI) microbiota with IBS is limited. We aimed to investigate the gut microbiota composition of SI and stool in IBS patients. MATERIALS AND METHODS: Biopsies of jejunum mucosa by balloon-assisted enteroscopy and faecal samples from 28 IBS patients and 19 healthy controls were analysed by next-generation sequencing method. RESULTS: The three major phyla in SI microbiota of case/control groups were Proteobacteria (32.8/47.7%), Bacteroidetes (25.2/15.3%), and Firmicutes (19.8/11.2%), and those of stool were Bacteroidetes (41.3/45.8%), Firmicutes (40.7/38.2%), and Proteobacteria (15.4/7.1%). Analysis based on the family level, IBS patients had a higher proportion of Veillonellaceae (mean proportion 6.49% versus 2.68%, p = 0.046) in stool than controls. Prevotellaceae was more abundant in IBS patients than in control group (14.27% versus 6.13%, p = 0.023), while Mycobacteriaceae (0.06% versus 0.17%, p = 0.024) and Neisseriaceae (6.40% versus 8.94%, p = 0.038) was less abundant in IBS patients' jejunal mucosa than those in controls. This less abundant jejunal Neisseriaceae was associated with more severe IBS (p = 0.03). The ratio of Firmicutes to Bacteroidetes in the stool of IBS-diarrhoea type patients was approximately three-fold higher, and the ratio of Firmicutes to Actinobacter in SI of IBS-mixed type patients was about nine-fold higher than healthy subjects. CONCLUSION: Higher abundance of colonic Veillonellaceae and SI Prevotellaceae, and lower amount of oral cavity normal flora in proximal SI were found in IBS patients. We may manipulate these bacteria in IBS patients in future studies (ClinicalTrial.gov Number NCT01679730).

In Vitro Activities of Tedizolid and Linezolid against Gram-Positive Cocci Associated with Acute Bacterial Skin and Skin Structure Infections and Pneumonia.

Tedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptible Staphylococcus aureus (MSSA) (n = 100), methicillin-resistant Staphylococcus aureus (MRSA) (n = 100), Streptococcus pyogenes (n = 50), Streptococcus agalactiae (n = 50), Streptococcus anginosus group (n = 75), Enterococcus faecalis (n = 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n = 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited better in vitro activities than linezolid against MSSA (MIC90s, 0.5 versus 2 µg/ml), MRSA (MIC90s, 0.5 versus 2 µg/ml), S. pyogenes (MIC90s, 0.5 versus 2 µg/ml), S. agalactiae (MIC90s, 0.5 versus 2 µg/ml), Streptococcus anginosus group (MIC90s, 0.5 versus 2 µg/ml), E. faecalis (MIC90s, 0.5 versus 2 µg/ml), and VRE (MIC90s, 0.5 versus 2 µg/ml). The tedizolid MICs against E. faecalis (n = 3) and VRE (n = 2) intermediate to linezolid (MICs, 4 µg/ml) were 1 µg/ml and 0.5 µg/ml, respectively. The tedizolid MIC90s against S. anginosus, S. constellatus, and S. intermedius were 0.5, 1, and 0.5 µg/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2- to 4-fold better in vitro activities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates of S. anginosus and S. constellatus than against those of S. intermedius in Taiwan were noted.

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

OBJECTIVES: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. DESIGN: Prospective, observational, multicenter study. SETTING, PATIENTS, AND INTERVENTIONS: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009). CONCLUSIONS: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

Antifungal susceptibilities of Candida isolates causing bloodstream infections at a medical center in Taiwan, 2009-2010.

We used the Sensititre YeastOne (SYO) method (Trek Diagnostic Systems) to determine the MICs of nine antifungal agents against 474 nonduplicate blood Candida isolates. The MIC results were interpreted according to updated clinical breakpoints (CBPs) recommended by the Clinical and Laboratory Standards Institute (CLSI; document M27-S4) or epidemiology cutoff values (ECVs). The rates of fluconazole susceptibility were 99.2% (234/236) in Candida albicans, 86.7% (85/98) in C. tropicalis, and 97.7% (42/43) in C. parapsilosis. Among the 77 isolates of C. glabrata, 90.9% showed dose-dependent susceptibility (S-DD) to fluconazole. Nearly all isolates of C. albicans, C. parapsilosis, and C. krusei were susceptible to voriconazole; however, rates of voriconazole susceptibility were 78.6% in C. tropicalis. Few isolates of C. albicans (n = 5; 2.1%) and C. glabrata (n = 3; 3.9%), no isolates of C. parapsilosis, C. krusei, and C. guilliermondii, but 62.2% (n = 51) of C. tropicalis isolates were non-wild type for posaconazole susceptibility. For itraconazole susceptibility, 98.3% of C. albicans isolates were wild type, and 3.9% (n = 3) of C. glabrata isolates were non-wild type. Almost all of the isolates tested (>97% for all species) were susceptible to both micafungin and anidulafungin. All isolates tested were found to be wild type for amphotericin B susceptibility, with MICs of <1 µg/ml. Further evaluation is needed to establish CBPs of antifungal agents by the 24-h SYO method for the management of patients with candidemia or other invasive candida infections.

Bruker biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of Nocardia, Rhodococcus, Kocuria, Gordonia, Tsukamurella, and Listeria species.

We evaluated whether the Bruker Biotyper matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system provides accurate species-level identifications of 147 isolates of aerobically growing Gram-positive rods (GPRs). The bacterial isolates included Nocardia (n = 74), Listeria (n = 39), Kocuria (n = 15), Rhodococcus (n = 10), Gordonia (n = 7), and Tsukamurella (n = 2) species, which had all been identified by conventional methods, molecular methods, or both. In total, 89.7% of Listeria monocytogenes, 80% of Rhodococcus species, 26.7% of Kocuria species, and 14.9% of Nocardia species (n = 11, all N. nova and N. otitidiscaviarum) were correctly identified to the species level (score values, ≥ 2.0). A clustering analysis of spectra generated by the Bruker Biotyper identified six clusters of Nocardia species, i.e., cluster 1 (N. cyriacigeorgica), cluster 2 (N. brasiliensis), cluster 3 (N. farcinica), cluster 4 (N. puris), cluster 5 (N. asiatica), and cluster 6 (N. beijingensis), based on the six peaks generated by ClinProTools with the genetic algorithm, i.e., m/z 2,774.477 (cluster 1), m/z 5,389.792 (cluster 2), m/z 6,505.720 (cluster 3), m/z 5,428.795 (cluster 4), m/z 6,525.326 (cluster 5), and m/z 16,085.216 (cluster 6). Two clusters of L. monocytogenes spectra were also found according to the five peaks, i.e., m/z 5,594.85, m/z 6,184.39, and m/z 11,187.31, for cluster 1 (serotype 1/2a) and m/z 5,601.21 and m/z 11,199.33 for cluster 2 (serotypes 1/2b and 4b). The Bruker Biotyper system was unable to accurately identify Nocardia (except for N. nova and N. otitidiscaviarum), Tsukamurella, or Gordonia species. Continuous expansion of the MALDI-TOF MS databases to include more GPRs is necessary.

Method-specific performance of vancomycin MIC susceptibility tests in predicting mortality of patients with methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: Emerging evidence shows that methicillin-resistant Staphylococcus aureus (MRSA) infections caused by isolates with higher vancomycin MICs within the susceptibility range are associated with adverse outcomes. No study, however, has examined different susceptibility tests in predicting treatment outcomes of MRSA infections. METHODS: This retrospective cohort study included 393 patients with MRSA bacteraemia. Vancomycin MICs for all MRSA isolates were determined simultaneously by agar dilution and the Etest, and using the MicroScan, VITEK-2 and Phoenix automated systems, and categorized into low- and high-MIC isolates at a breakpoint of ≥ 2 mg/L. The essential and categorical agreement between testing methods was compared. The method-specific ability to predict in-hospital mortality was examined by multivariate logistic regression analysis controlling for other potential confounders using clinical data from 310 vancomycin-treated MRSA bacteraemia patients. RESULTS: The agar dilution, Etest, MicroScan, VITEK-2 and Phoenix methods assessed 14.2% (56/393), 9.7% (38/393), 28.8% (113/393), 22.6% (89/393) and 3.1% (12/393) of MRSA isolates as having high (≥ 2 mg/L) vancomycin MICs. The essential and categorical agreement between testing methods ranged from 98.5% to 100% and from 73.8% to 91.9%, respectively. High vancomycin MICs for isolates determined using agar dilution and the Etest independently predicted mortality when controlling for confounding factors [adjusted OR, 2.321; 95% CI, 1.160-4.641; and adjusted OR, 3.121; 95% CI, 1.293-7.536, respectively]. High vancomycin MICs determined using all three automated systems failed to predict mortality. CONCLUSIONS: Vancomycin MICs generated by the agar dilution and Etest methods, but not the automated systems, independently predicted mortality among vancomycin-treated MRSA bacteraemia patients. Clinicians should incorporate this information with clinical assessment for decisions on appropriate anti-MRSA treatment.

Decline in the incidence of invasive pneumococcal disease at a medical center in Taiwan, 2000-2012.

BACKGROUND: It is essential to investigate the serotype distribution of pneumococcal diseases in each region and its associated clinical features. This study investigated the annual incidence of invasive pneumococcal disease (IPD) and the distribution of serotypes of isolates causing IPD at a medical center in northern Taiwan during the period 2000 to 2012. METHODS: Serotypes of all available Streptococcus pneumoniae isolates causing IPD were determined using the latex agglutination test. RESULTS: During the study period, the annual incidence (per 10,000 admissions) of IPD decreased significantly from 9.8 in 2000 to 2.1 in 2012 (P < 0.001). The annual incidence of all-cause bacteremia, primary pneumococcal bacteremia, bacteremic pneumonia, peritonitis, and meningitis also decreased significantly during the study period (P < 0.05). In contrast to the decrease in annual incidence of pneumococcal serotypes 14, 23F and 6B, the incidence and the proportion of serotype 19A significantly increased with time (P < 0.001). The coverage rate of 7-valent protein conjugated vaccine (PCV-7) and PCV-10 decreased significantly; however, the coverage rate of PCV-13 and pneumococcal polysaccharide vaccine (PPV-23) remained stable over time. Serotype 14 and 19A isolates were commonly isolated from blood and pleural effusion, respectively. Serotypes 14 and 23F were the two most common serotypes found in adult patients, and serotypes 14 and 19A were the two most common serotypes isolated from children. CONCLUSIONS: Although the incidence of IPD has decreased, serotype 19A is an emerging problem in Taiwan. The distribution of serotypes of pneumococci varied with clinical symptoms and age. As the changing distribution of pneumococcal serotype with time, the coverage rate of pneumococcal vaccines would be different.

Increase in the rate of azithromycin-resistant Streptococcus pneumoniae isolates carrying the erm(B) and mef(A) genes in Taiwan, 2006-2010.

BACKGROUND: This study investigated the molecular characteristics of azithromycin-resistant Streptococcus pneumoniae in Taiwan. METHODS: A total of 486 non-duplicate isolates of azithromycin-resistant S. pneumoniae recovered from various clinical sources of patients treated at 22 different hospitals in Taiwan from 2006 to 2010. The presence of erm(B) and mef(A) genes using duplex PCR, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis of these isolates were studied. RESULTS: Of the isolates tested, 59% carried the erm(B) gene, 22% carried the mef(A) gene, and 19% carried both genes. The prevalence of isolates carrying the erm(B) and mef(A) genes increased from 10% (11/110) in 2006 to 25% (15/60) in 2010 (p-value = 0.0136). The majority of isolates carrying both erm(B) and mef(A) genes belonged to serotypes 19 F (64%) followed by 19 F A (24%). Of these isolates, 33% were sequence type 320 (ST320), 32% were ST236, and 12% were ST271. CONCLUSIONS: The increase in incidence of mef(A)/erm(B)-positive azithromycin-resistant S. pneumoniae isolates during the study period was primarily due to serotypes 19 F and 19A and ST236 and ST320.

Daptomycin-loaded polymethylmethacrylate bone cement for joint arthroplasty surgery.

Antibiotic-loaded acrylic bone cement has been frequently used as an infection prophylaxis or antibiotic-loaded spacer in infected arthroplasty. In addition, daptomycin has been used recently against broad spectrum Gram-positive organisms. The goal of this in vitro study is to investigate the bacteriacidal and mechanical properties of daptomycin-incorporated polymethylmethacrylate (PMMA) bone cement and evaluate its feasibility for clinical use. Daptomycin (0.5, 1, or 2 g) was premixed with 40 g of PMMA bone cement powder before curing. The mechanical properties of the daptomycin-loaded acrylic bone cement (DLABC) were estimated following standard guidance, and the release profile and kinetics of daptomycin from PMMA were analyzed. The antimicrobial efficacy of DLABC was determined with a zone of inhibition (ZOI) assay against Staphylococcus aureus, Staphylococcus epidermis, Enterococcus faecalis, and Enterococcus faecium, respectively. The results showed that the compressive strength, of PMMA bone cement, which was higher than 100 MPa in all groups, was sufficient according to ISO 5833 after incorporation of daptomycin. The encapsulated daptomycin was released for 2 weeks with a 9.59 ± 0.85%, 15.25 ± 0.69%, and 20.64 ± 20.33% released percentage on the first day in the low, mid, and high groups, respectively. According to the calculated release kinetics, incorporated daptomycin should be 3.3 times the original dose to double its release. Although all recipes of DLABC had a microbial inhibitory effect, the effect with a higher encapsulated amount of daptomycin was more significant. Therefore, we believe that daptomycin can be locally delivered from PMMA bone cement at the surgical site as a prophylactic or treatment for osteomyelitis against Gram-positive organisms with intact cement function.