Pao-Yu Chen

Effect of Daptomycin Dose on the Outcome of Vancomycin-Resistant, Daptomycin-Susceptible Enterococcus faecium Bacteremia

Background Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined. Methods We conducted a prospective, observational, cohort study during 2010-2015. We included patients who received a daptomycin dose of ≥6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis. Results We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ≤2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7-9 mg/kg, and 5/25 (20%) for a dose of ≥9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25-49.62; P=.003) and 7-9 mg/kg (aOR, 5.01; 95% CI, 1.14-21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase. Conclusion Higher daptomycin doses (≥9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment.

Envelope gene sequences of human T-lymphotropic virus type I in Taiwan

SummaryThree major types of HTLV-I had been proposed, the Melanesian type, the Zairian type, and the cosmopolitan type, which was further divided into subtypes A, B and C, according to the phylogenetic tree constructed from LTR sequences of current HLTV-I isolates. In this study, the envelope gene sequences of HTLV-I from 9 Taiwanese were analyzed. Based on the phylogenetic tree constructed by unweighed pair group method and the sequence homology analysis by GCG computer programs, the envelope gene sequences of HTLV-I proviruses from these 9 Taiwanese belonged to subtype A or subtype B of the cosmopolitan type and were closely related to HTLV-I from Japan. Twelve subtype-specific nucleotide variations were deduced from the comparison of complete or partial envelope gene sequences of 16 HTLV-I isolates of known subtypes as well as those of 9 Taiwanese. These data provided the basis for subtyping the cosmopolitan type of HTLV-I by amplification of envelope gene sequences and restriction fragment length polymorphism studies. A more extensive survey based upon this proposal was warranted.

Etiology of pulmonary complications of human immunodeficiency virus-1-infected patients in Taiwan in the era of combination antiretroviral therapy: A prospective observational study

OBJECTIVES We aimed to investigate the etiology of pulmonary complications of human immunodeficiency virus-(HIV)-1-infected patients in Taiwan in the era of combination antiretroviral therapy (cART). METHODS From July 2009 to March 2012, a prospective observational study was conducted to identify the etiology of pulmonary complications in HIV-1-infected patients who sought HIV care at a university hospital in Taiwan. A stepwise diagnostic approach was adopted, which included radiography, serology, microbiology, bronchoscopy or video-assisted thoracoscopic surgery, and polymerase chain reaction assays for cytomegalovirus and Pneumocystis jirovecii. RESULTS During the study period, a total of 203 episodes of pulmonary complications that occurred in 190 patients with a mean CD4 count of 123 × 10(6) cells/L were analyzed. Thirty-eight episodes (18.7%) occurred in patients with a CD4 count >200 × 10(6) cells/L, 71 (35.0%) between 50 and 200 × 10(6) cells/L, and 94 (46.3%) <50 × 10(6) cells/L. Pneumocystis pneumonia accounted for more than half of the complications in patients with a CD4 count <200 × 10(6) cells/L. In patients with a CD4 count >200 × 10(6) cells/L, the etiology of pulmonary complications was diverse, with bacterial infections (47.4%) being the most common, followed by tuberculosis (15.8%) and lung edema (13.2%). Pneumocystosis and cytomegalovirus pneumonitis were seen mostly or exclusively in patients with a CD4 count <200 × 10(6) cells/L and were the leading causes of interstitial pneumonitis. On the other hand, empyema, legionellosis, and lung edema were more commonly seen in patients with a CD4 count >200 × 10(6) cells/L. CONCLUSIONS The etiology of pulmonary complications in HIV-1-infected patients was diverse and varied with the categories of CD4 counts. Pneumocystosis remained the leading cause of pulmonary complications in patients with lower CD4 counts in Taiwan in the cART era.

Increasing resistance to fusidic acid among clinical isolates of MRSA

References 1 Flamm RK, Mendes RE, Hogan PA et al. Linezolid surveillance results for the United States (LEADER Surveillance Program 2014). Antimicrob Agents Chemother 2016; 60: 2273–80. 2 Shen J, Wang Y, Schwarz S. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J Antimicrob Chemother 2013; 68: 1697–706. 3 Wang Y, Lv Y, Cai J et al. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J Antimicrob Chemother 2015; 70: 2182–90. 4 Brenciani A, Morroni G, Vincenzi C et al. Detection in Italy of two clinical Enterococcus faecium isolates carrying both the oxazolidinone and phenicol resistance gene optrA and a silent multiresistance gene cfr. J Antimicrob Chemother 2016; 71: 1118–9. 5 Li D, Wang Y, Schwarz S et al. Co-location of the oxazolidinone resistance genes optrA and cfr on a multiresistance plasmid from Staphylococcus sciuri. J Antimicrob Chemother 2016; 71: 1474–8.

Impact of prior healthcare-associated exposure on clinical and molecular characterization of methicillin-susceptible Staphylococcus aureus bacteremia: results from a retrospective cohort study.

AbstractBy virtue of medical advances and an aging society, people have increased opportunities for healthcare exposure. Little is known about the impact of healthcare exposure on the clinical features and molecular typing of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We classified the onset of MSSA bacteremia into 3 mutually exclusive categories according to the Centers for Disease Control definition, and conducted a retrospective cohort study to investigate the differences among patients with community-associated (CA), healthcare-associated community onset (HACO), and hospital onset (HO) MSSA bacteremia at a medical center from January 1, 2002 through December 31, 2011. Antibiotic susceptibilities and multilocus sequence typing of MSSA isolates were also determined.A total of 290 patients with MSSA bacteremia, including of 165 (56.9%), 91 (31.4%), and 34 (11.7%) of HACO, HO, and CA, respectively, were studied. ST188 (29.3%) was the most common sequence type regardless of classification. Patients with HACO bacteremia were significantly older, had more solid tumors, higher Charlson scores, and more catheter-related bloodstream infections than those with CA bacteremia. The proportions of osteoarticular infections among patients with both HACO and CA bacteremia were higher than that of patients with HO bacteremia. By univariate analysis, patients with HO bacteremia had significantly higher in-hospital mortality compared to those with CA or HACO bacteremia (31.9% vs 18.8% and 20.4%). Multivariate analysis showed that Charlson score (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.10–1.52), septic shock (OR, 5.28; 95% CI, 2.37–11.78), liver cirrhosis (OR, 3.57; 95% CI, 1.14–11.24), receipt of &bgr;-lactams other than oxacillin and cefazolin as definitive therapy (OR, 9.27; 95% CI, 4.25–20.23), and higher oxacillin minimum inhibitory concentration (MIC) (≥0.5 mg/L) (OR, 2.35; 95% CI, 1.05–5.25) of the causative pathogen were independently associated with in-hospital mortality.In conclusion, patients with HACO bacteremia had different host factors compared with those with CA bacteremia. Infection foci varied with different onset settings. Overall, ST188 was the most predominant sequence type. Onset settings were not independently associated with outcomes.

Subtyping of human T-lymphotropic virus type I by amplification of long terminal repeat sequences and restriction fragment length polymorphism analysis in carriers with multiple transfusions

Abstract Five major subtypes of human T-lymphotropic virus type I (HTLV-I) have been proposed: cosmopolitan, Japanese, West African, Central African, and Melanesian. Based on nucleotide variations specific to particular subtypes, it was possible to genotype HTLV-I rapidly by restriction fragment length polymorphism (RFLP) studies following polymerase chain reaction (PCR) . In this study, the restriction patterns of two LTR fragments were analyzed using eight restriction endonucleases (AvaI, Eco57I, BsoFI, NdeI, SacI, DraI, MaeII, and MaeIII). Genotyping of HTLV-I was done in nine patients with adult T-cell leukemia or HTLV-I-associated myelopathy/tropical spastic paraparesis, in three prostitutes, and in 19 carriers with multiple transfusion in Taiwan. The subtyping results of RFLP studies using these eight restriction endonucleases were in accordance with those of phylogenetic analysis. A substitution of G by A at nucleotide position 503, which creates the DraI site but suppresses the SacI site, was found not only in the Japanese subtype but also in a minority of the cosmopolitan subtype. A mutation near the position of subtype-specific nucleotide variations might suppress the restriction site and lead to unexpected restriction patterns. Amplification of more than one proviral fragment and RFLP studies with a group of appropriate restriction endonucleases may provide rapid and accurate genotyping of HTLV-I. More carriers are required to evaluate the possibility of mixed infection with different HTLV-I subtypes.

A retrospective clinical comparison of daptomycin vs daptomycin and a beta-lactam antibiotic for treating vancomycin-resistant Enterococcus faecium bloodstream infections

There is limited clinical evidence to support the combination of daptomycin and beta-lactam antibiotics (DAP + BLA) for treatment of vancomycin-resistant enterococci (VRE) bloodstream infections (BSI). We conducted a prospective observational cohort study of VRE-BSI during 2010–2015. The primary endpoint was mortality at the end of treatment. We included 114 patients who received DAP for VRE-BSI. Of these 87 (76.3%) received DAP + BLA. There were no significant differences in mortality between the DAP and DAP + BLA groups on univariable analysis (10/27 vs. 34/87, P = 0.85). A subgroup analysis of patients with enterococcal DAP minimum inhibitory concentrations (MICs) ≤2 mg/L, revealed that those treated with DAP + BLA had a lower mortality (adjusted hazard ratio [aHR], 0.23; 95% confidence interval [CI], 0.06–0.93; P = 0.04) after adjustment for other significant predictors of mortality, including the DAP dose. In addition, patients receiving high-dose (≥9 mg/kg) DAP + BLA independently had a better survival than those receiving low-dose DAP alone (aHR = 5.16), low-dose DAP + BLA (aHR = 5.39), and high-dose DAP alone (aHR = 19.01) (P < 0.05 for all comparisons). For patients with VRE-BSIs, the DAP MIC of the isolate and the DAP dose influence the effect of DAP + BLA on outcome. A high-dose DAP + BLA might improve survival. These findings support the use of high-dose DAP + BLA for treatment of VRE-BSI.

Effectiveness of echinocandins versus fluconazole for treatment of persistent candidemia: a time-dependent analysis

OBJECTIVES Echinocandins are fungicidal and more active than fluconazole against Candida biofilms. This is known to be an important mechanism for Candida persistence. However, there is limited evidence of effectiveness of echinocandins for treating persistent candidemia. METHODS We prospectively observed adult patients with persistent candidemia from March 2011 to February 2016. This was defined as the isolation of the same Candida species for ≥ 5 days from blood cultures. We used a time-dependent analysis to evaluate the impact of definitive therapy on mycological eradication and overall survival at 30 days from the index date (the date of collecting the second positive blood culture). RESULTS We screened 1162 episodes of candidemia. Of 196 non-duplicate patients enrolled, 64 received echinocandins and 132 received fluconazole as their first definitive therapy after the index date. The rates of mycological eradication and overall survival were 67.3% and 55.6%, respectively. The factors associated with mycological eradication included receipt of an echinocandin as the definitive therapy, adequate source control, and not receiving parenteral hyperalimentation. The factors related to overall survival were APACHE II, not receiving corticosteroids, and receiving cardiovascular or abdominal surgery. CONCLUSIONS Echinocandins were more effective than fluconazole in achieving mycological eradication in patients with persistent candidemia.