Ching-Lan Lu

Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin determined by agar dilution and disk diffusion methods.

ABSTRACT We studied the antimicrobial activity of fosfomycin against 960 strains of commonly encountered bacteria associated with urinary tract infection using standard agar dilution and disk diffusion methods. Species studied included 3 common species of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia; methicillin-susceptible and -resistant Staphylococcus aureus; and vancomycin-susceptible and resistant Enterococcus faecalis and E. faecium. MICs and inhibition zone diameters were interpreted in accordance with both the currently recommended Clinical and Laboratory Standards Institute (CLSI) criteria for urinary tract isolates of Escherichia coli and Enterococcus faecalis and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria for Enterobacteriaceae. Tentative zone diameter interpretive criteria were developed for species not currently published by CLSI or EUCAST. Escherichia coli was uniformly susceptible to fosfomycin, as were most strains of Klebsiella pneumoniae and Enterobacter cloacae. A. baumannii was resistant to fosfomycin, while the prevalence of resistance in P. aeruginosa and S. maltophilia was greatly affected by the choice of MIC breakpoint. New tentative zone diameter criteria for K. pneumoniae, E. cloacae, S. aureus, and E. faecium were able to be set, providing some interim laboratory guidance for disk diffusion until further breakpoint evaluations are undertaken by CLSI and EUCAST.

Correlation between antibiotic consumption and resistance of Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009

OBJECTIVES This study investigated the correlation between antibiotic consumption and antimicrobial resistance in Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. METHODS Disc susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative bacilli causing healthcare-associated infections were evaluated. Data on annual patient-days and annual consumption (defined daily doses per 1000 patient-days) of extended-spectrum cephalosporins, β-lactam/β-lactamase inhibitor combinations, carbapenems, aminoglycosides and fluoroquinolones were analysed. RESULTS The trend of total consumption of extended-spectrum cephalosporins, β-lactam/β-lactamase inhibitor combinations, carbapenems, aminoglycosides and fluoroquinolones significantly increased between 2000 and 2003 and remained stable between 2004 and 2009. The decreasing use of gentamicin and amikacin in recent years was associated with increasing susceptibility of E. coli, E. cloacae, S. marcescens and P. aeruginosa to gentamicin, as well as increasing susceptibility of P. aeruginosa to amikacin. The use of piperacillin/tazobactam was positively correlated with the prevalence of piperacillin/tazobactam-resistant E. coli and S. maltophilia. In contrast, the use of cefotaxime and piperacillin/tazobactam was negatively correlated with the prevalence of cefotaxime-resistant E. coli and piperacillin/tazobactam-resistant S. maltophilia, respectively. The consumption of fluoroquinolones was positively correlated with the rates of ciprofloxacin-resistant E. coli, piperacillin/tazobactam-resistant P. aeruginosa and ceftazidime-resistant S. maltophilia. CONCLUSIONS The relationship between antibiotic prescription and the rates of resistance for Gram-negative bacteria is complicated; every type of antimicrobial agent or even individual agent can have distinct associations with different pathogens.

Recent Hepatitis C Virus Infections in HIV-Infected Patients in Taiwan: Incidence and Risk Factors

ABSTRACT Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-infected men who have sex with men (MSM) in Europe, Australia, and North America. Little is known concerning whether this also occurs in other Asia-Pacific countries. Between 1994 and 2010, a prospective observational cohort study was performed to assess the incidence of recent HCV seroconversion in 892 HIV-infected patients (731 MSM and 161 heterosexuals) who were not injecting drug users. A nested case-control study was conducted to identify associated factors with recent HCV seroconversion, and phylogenetic analysis was performed using NS5B sequences amplified from seroconverters. During a total followup duration of 4,270 person-years (PY), 30 patients (3.36%) had HCV seroconversion, with an overall incidence rate of 7.03 per 1,000 PY. The rate increased from 0 in 1994 to 2000 and 2.29 in 2001 to 2005 to 10.13 per 1,000 PY in 2006 to 2010 (P < 0.05). After adjustment for age and HIV transmission route, recent syphilis remained an independent factor associated with HCV seroconversion (odds ratio, 7.731; 95% confidence interval, 3.131 to 19.086; P < 0.01). In a nested case-control study, seroconverters had higher aminotranferase levels and were more likely to have CD4 ≥ 200 cells/μl and recent syphilis than nonseroconverters (P < 0.05). Among the 21 patients with HCV viremia, phylogenetic analysis revealed 7 HCV transmission clusters or pairs (4 within genotype 1b, 2 within genotype 2a, and 1 within genotype 3a). The incidence of HCV seroconversion that is associated with recent syphilis is increasing among HIV-infected patients in Taiwan.

Metabolic syndrome among HIV-infected Taiwanese patients in the era of highly active antiretroviral therapy: prevalence and associated factors

OBJECTIVES Metabolic complications related to antiretroviral therapy are rarely investigated among HIV-infected patients in Asian countries. We investigated the prevalence of and factors associated with metabolic syndrome among HIV-infected patients who are ethnic Chinese in the era of highly active antiretroviral therapy (HAART). METHODS A cross-sectional survey was performed to collect information on the demographic and clinical characteristics and antiretroviral therapy prescribed in 877 HIV-infected patients at a university hospital in Taiwan from May 2008 to April 2009. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome after adjusting for the waist circumference criteria for Asians. RESULTS Of the 877 patients, 75.3% were male homosexuals, 80.7% were receiving HAART and 88.7% had CD4 counts ≥ 200 cells/mm(3). Metabolic syndrome was diagnosed in 210 patients (26.2%). After adjusting for age, gender, smoking status, family history of diabetes mellitus, cardiovascular disease and hypertension, and baseline CD4 and plasma HIV RNA load, use of protease inhibitors (PIs) was significantly associated with the presence of metabolic syndrome (OR 1.63; 95% CI 1.10-2.43). In addition, exposure to PI for ≥ 3 years, to HAART for ≥ 6 years and to nucleoside reverse transcriptase inhibitor(s) for ≥ 6 years was significantly associated with the presence of metabolic syndrome with an adjusted OR of 1.96 (95% CI 1.13-3.42), 1.78 (95% CI 1.03-3.07), and 1.91 (95% CI 1.11-3.30), respectively. CONCLUSIONS Approximately one-fourth of HIV-infected Taiwanese patients developed metabolic syndrome in the HAART era. Receipt of HAART and prolonged exposure to PI and nucleoside reverse transcriptase inhibitor(s) were associated with metabolic syndrome.

Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus–infected and -uninfected men who have sex with men†‡§

The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)‐infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV‐uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV‐infected MSM received either two doses of HAV vaccine (1,440 enzyme‐linked immunosorbent assay units) (n = 140) with the second dose given at week 24 or three doses (n = 225) with the second and third dose given at weeks 4 and 24, respectively, while HIV‐uninfected MSM (n = 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti‐HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention‐to‐treat analysis for two‐dose HIV‐infected, three‐dose HIV‐infected, and two‐dose HIV‐uninfected MSM, respectively. The GMC of anti‐HAV antibody at week 48 for three‐dose HIV‐infected MSM (2.29 ± 0.73 log10 mIU/mL) was significantly higher than that for two‐dose HIV‐infected MSM (1.94 ± 0.66; P < 0.01), but was lower than HIV‐uninfected MSM (2.49 ± 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/μL increase, 1.13; 95% confidence interval [CI], 1.05‐1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10‐3.28) before HAV vaccination were predictive of seroconversion in HIV‐infected patients. Conclusion: Serologic response rate to three and two doses of HAV vaccine was similar in HIV‐infected MSM, which was lower than that in HIV‐uninfected MSM receiving two doses. HAV vaccination in HIV‐infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate. (HEPATOLOGY 2013)

Correlation between antimicrobial consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009

This study investigated the correlation between antibiotic consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. Overall, the trend of total consumption (defined daily dose [DDD] per 1,000 patient-days) of glycopeptides, including vancomycin and teicoplanin, significantly increased during 2000 to 2003 and remained stable during 2004–2009. Vancomycin consumption significantly increased during 2003 and decreased after 2004. A significant decrease in the resistance rate with time was found for oxacillin- and gentamicin-resistant S. aureus. In contrast, the rates of vancomycin- and teicoplanin-resistant enterocci increased significantly. A significant correlation was found between the increased use of extended-spectrum cephalosporins, β-lactam-β-lactamase inhibitor combinations, carbapenems and the decreased prevalence of methicillin-resistant S. aureus (MRSA). In contrast, the increased use of teicoplanin, extended-spectrum cephalosporins, β-lactam-β-lactamase inhibitor combinations, and carbapenems was correlated with the increased prevalence of vancomycin-resistant enterococci (VRE). In conclusion, this 10-year study in a single institution identified different correlations between the prescription of antibiotics and the resistance rates of MRSA and VRE. Strict implementation of infection control policy based on these correlates would be helpful in decreasing the presence of these multidrug-resistant pathogens in hospitals.

Microbiological and clinical characteristics of vancomycin-resistant Enterococcus faecium bacteraemia in Taiwan: implication of sequence type for prognosis

OBJECTIVES Vancomycin-resistant enterococci (VRE), particularly vancomycin-resistant Enterococcus faecium (VREfm), have emerged among the leading pathogens causing hospital-acquired infections worldwide. We aimed to examine whether there were newly introduced clones contributing to this increase and to assess the risk factors for mortality in patients with VREfm bacteraemia. METHODS Between 2003 and 2010, all medical records of adult patients diagnosed with VREfm bacteraemia at a university hospital in Taiwan were reviewed. Antibiotic susceptibility, genotyping and multilocus sequence typing of the VREfm isolates were performed. RESULTS During the study period, the prevalence of non-duplicated blood VRE isolates increased significantly from 3.9% in 2003 to 18.9% in 2010 (P < 0.0001). One-hundred-and-forty-nine patients with VREfm bacteraemia were noted and 102 isolates of VREfm were available for microbiological characterization. All isolates were susceptible to daptomycin and linezolid. Sequence type (ST) 18 and ST414 were the two predominant emerging STs from 2009 to 2010, accounting for 29.7% and 25.0% of all isolates, respectively. Patients who received immunosuppressives, had a high Charlson comorbidity index or experienced septic shock had a significantly higher 14 day mortality rate. Patients who had bacteraemia caused by ST414 isolates and received appropriate antibiotics had a lower 14 day mortality rate. CONCLUSIONS The prevalence of the VRE that caused bacteraemia increased from 2003 to 2010. This increase might be attributed to the clonal spread of VREfm belonging to ST18 and ST414. The all-cause 14 day mortality rate was lower in patients with bacteraemia due to VREfm isolates that belonged to ST414.

Trends of transmitted drug resistance of HIV-1 and its impact on treatment response to first-line antiretroviral therapy in Taiwan

OBJECTIVES To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated. METHODS Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case-control study was conducted to assess the impact of TDR on treatment outcomes. RESULTS The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003-06 to 5.1% in 2007-10. In the matched case-control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS >2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P < 0.001). In patients receiving regimens with GSS ≤2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06-1.12, P = 0.07). CONCLUSIONS In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤2.5 was associated with poorer treatment responses than regimens with GSS >2.5.

Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy.

Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART). Methods: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes. Results: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23–4.78] and 3.58 [95% CI. 1.76–7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60–3.64] and 3.62 [95% CI, 1.11–11.81], respectively). Conclusions: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses.

Revaccination with 7-valent pneumococcal conjugate vaccine elicits better serologic response than 23-valent pneumococcal polysaccharide vaccine in HIV-infected adult patients who have undergone primary vaccination with 23-valent pneumococcal polysaccharide vaccine in the era of combination antiretroviral therapy

HIV-infected adults who had received 23-valent pneumococcal polysaccharide vaccine (PPV23) five years or more earlier consecutively underwent revaccination with one dose of PPV23 (127 subjects) from December 2005 through October 2007, or upon change in standard of care, non-randomly one (50) or two doses (44) of 7-valent pneumococcal conjugate vaccine (PCV7) from October 2008 through June 2010. Serologic response was defined as ≥ 2-fold increase in the IgG level plus a level ≥ 1000ng/ml 48 weeks following revaccination. At week 48, the response rate was significantly higher in the 2-dose PCV7 group compared with that in the 1-dose PCV7 or PPV23 group (63.6% vs 32.0% vs 8.7%, respectively; P<0.05). Revaccination with one dose of PCV7 (AOR, 4.57), two doses of PCV7 (AOR, 22.66), and CD4 >350 cells/μl (AOR, 3.24) and undetectable viral load (AOR, 3.87) at revaccination were statistically significantly associated with a better serologic response at week 48. Despite the limitation that study arms were neither randomized nor contemporaneous, we conclude that revaccination with PCV7 appears to elicit a better serologic response than PPV23 in the HIV-infected adults who have received PPV23 five years or more earlier (clinical trial registration number: NCT00885625).