Hung Jen Tang

Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009-2010 results from the Study for Monitoring Antimicrobial Resistance Trends (SMART)

In 2009, the Study for Monitoring Antimicrobial Resistance Trends (SMART) was expanded to include surveillance of Gram-negative pathogens causing urinary tract infections (UTIs) in the Asia-Pacific region. A total of 1762 isolates were collected from 38 centers in 11 countries from patients with UTIs in 2009 and 2010. In vitro susceptibilities were determined by the broth microdilution method and susceptibility profiles were determined using minimum inhibitory concentration (MIC) interpretive criteria, as recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2010 (M100-S20), in 2011 (M100-S21), and in 2012 (M100-S22). Enterobacteriaceae comprised 86.0% of the isolates, of which Escherichia coli (56.5%) and Klebsiella pneumoniae (13.8%) were the two most common species. Amikacin was the most effective antibiotic (91.7%), followed by ertapenem (86.9%), imipenem (86.6%), and piperacillin-tazobactam (84.9%). Rates of susceptibility were 50.3% for cefoxitin and ranged from 50.3% to 74.2% for the third- and fourth-generation cephalosporins. For ciprofloxacin and levofloxacin, the susceptibility rates were 51.4% and 54.4%, respectively. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae comprised 28.2% of all isolates. We also found a high rate of resistance to carbapenems among Acinetobacter baumannii and Pseudomonas aeruginosa causing UTI. Interestingly, according to 2012 CLSI breakpoints, approximately 33.4% of ESBL producers were still susceptible to ceftazidime. However, this in vitro efficacy of ceftazidime needs to be validated in vivo by clinical data. The lowered CLSI interpretive breakpoints for piperacillin-tazobactam, carbapenems, and some cephalosporins in 2011-2012 for Enterobacteriaceae resulted in an approximate 5% drop in susceptibility rates for each drug, with the exception of imipenem for which the susceptibility rate dropped from 99.4% according to 2010 criteria to 91.2% according to 2011 criteria. With the updated CLSI criteria, the antimicrobial resistance threat from UTI pathogens in the Asia Pacific area was revealed to be more prominent.

Vibrio vulnificus in Taiwan

Clinical features of 84 patients with V. vulnificus infection are analyzed and molecular features of isolates are described.

Impact of revised CLSI breakpoints for susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2002–2010

This study examined the rates of susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates that had been obtained from patients with intraabdominal infections in the Asia-Pacific region as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Susceptibility profiles obtained using 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints were compared with those obtained using the 2011 CLSI breakpoints. From 2002 to 2010, Escherichia coli and Klebsiella pneumoniae together accounted for more than 60% of the 13714 Enterobacteriaceae isolates analyzed during the study period. Extended-spectrum β-lactamase (ESBL) producers comprised 28.2% of E. coli isolates and 22.1% of K. pneumoniae isolates in the Asia-Pacific region, with China (55.6% and 33.7%, respectively) and Thailand (43.1% and 40.7%, respectively) having the highest proportions of ESBL producers. Based on the 2011 CLSI criteria, 77.2% of the Enterobacteriaceae isolates, 40.4% of ESBL-producing E. coli, and 25.2% of ESBL-producing K. pneumoniae isolates were susceptible to ceftazidime. Carbapenems showed in vitro activity against >90% of Enterobacteriaceae isolates in all participating countries, except for ertapenem in South Korea (susceptibility rate 82.2%). Marked differences (>5%) in susceptibility of ESBL-producing E. coli and K. pneumoniae isolates to carbapenems were noted between the profiles obtained using the 2009 CLSI criteria and those using the 2011 CLSI criteria. Continuous monitoring of antimicrobial resistance is necessary in the Asia-Pacific region.

In vitro susceptibilities of non-Enterobacteriaceae isolates from patients with intra-abdominal infections in the Asia-Pacific region from 2003 to 2010: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART)

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained <48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB.

In vitro efficacy of antimicrobial agents against high-inoculum or biofilm-embedded meticillin-resistant Staphylococcus aureus with vancomycin minimal inhibitory concentrations equal to 2 μg/mL (VA2-MRSA)

Minimal inhibitory concentration (MIC) creep in meticillin-resistant Staphylococcus aureus (MRSA) isolates has been observed in recent years. The potential roles of vancomycin-based combination regimens as well as linezolid and tigecycline against five clinical MRSA isolates with vancomycin MICs of 2 μg/mL (VA2-MRSA) were evaluated and compared in vitro. Antimicrobial susceptibility was studied by the agar dilution method. Anti-MRSA activities of linezolid, tigecycline, vancomycin, minocycline, rifampicin and fosfomycin alone as well as of three vancomycin-based combinations were studied by time-kill method and using a biofilm model. When VA2-MRSA at an inoculum of 1×10(5)colony-forming units (CFU)/mL was incubated with vancomycin, tigecycline, linezolid or rifampicin alone, bactericidal activity lasted for 48 h in time-kill analysis. At a higher inoculum of 1×10(7) CFU/mL, only linezolid demonstrated a bacteriostatic effect at 24 h and the inhibitory activity lasted for 36 h. However, bacterial growth was inhibited ≥2log(10) at 24 h and was even undetectable at 48 h with vancomycin plus fosfomycin or rifampicin. In biofilm studies, vancomycin plus fosfomycin or minocycline at susceptible breakpoint concentrations demonstrated an enhanced antibacterial effect comparable with linezolid and better than tigecycline. In conclusion, vancomycin plus fosfomycin or rifampicin exhibited a synergistic and better antibacterial effect than linezolid or tigecycline alone against high-inoculum planktonic VA2-MRSA. Vancomycin plus fosfomycin or minocycline compared with linezolid exhibited a similar inhibitory effect, better than tigecycline alone, against biofilm-embedded VA2-MRSA. Evaluating the toxicity and efficacy of high-dose vancomycin monotherapy for VA2-MRSA, the fosfomycin combination exhibited a rapid killing effect in both conditions and may provide another therapeutic choice.

In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

ABSTRACT To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

Comparison of serological response to doxycycline versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients: a multi-center observational study.

Background While doxycycline is recommended as an alternative treatment of syphilis in patients with penicillin allergy or intolerance, clinical studies to compare serological response to doxycycline versus benzathine penicillin in treatment of early syphilis among HIV-infected patients remain sparse. Methods We retrospectively reviewed the medical records of HIV-infected patients with early syphilis who received doxycycline 100 mg twice daily for 14 days (doxycycline group) and those who received 1 dose of benzathine penicillin (2.4 million units) (penicillin group) between 2007 and 2013. Serological responses defined as a decline of rapid plasma reagin titer by 4-fold or greater at 6 and 12 months of treatment were compared between the two groups. Results During the study period, 123 and 271 patients in the doxycycline and penicillin group, respectively, completed 6 months or longer follow-up. Ninety-one and 271 patients in the doxycycline and penicillin group, respectively, completed 12 months or longer follow-up. Clinical characteristics were similar between the two groups, except that, compared with penicillin group, doxycycline group had a lower proportion of patients with secondary syphilis (65.4% versus 41.5%, P<0.0001) and a higher proportion of patients with early latent syphilis (25.3% versus 49.6%, P<0.0001). No statistically significant differences were found in the serological response rates to doxycycline versus benzathine penicillin at 6 months (63.4% versus 72.3%, Pu200a=u200a0.075) and 12 months of treatment (65.9% versus 68.3%, Pu200a=u200a0.681). In multivariate analysis, secondary syphilis, but not treatment regimen, was consistently associated with serological response at 6 and 12 months of follow-up. Conclusions The serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary syphilis were more likely to achieve serological response than those with other stages.

One Dose versus Three Weekly Doses of Benzathine Penicillin G for Patients Co-Infected with HIV and Early Syphilis: A Multicenter, Prospective Observational Study

Background One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited. Methods We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3–6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%. Results Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4–72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3–79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17–3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38–2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20–2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively. Conclusions Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.

Incidence of Aeromonas bacteremia in Southern Taiwan: Vibrio and Salmonella bacteremia as comparators

The aim of the investigation was to describe the incidence of Aeromonas bacteremia in a city with a population of about 1.87 million inhabitants, located in southern Taiwan, between 2008 and 2010. Such data were compared with the incidences of Vibrio and Salmonella bacteremia in the same period and the incidence of Aeromonas bacteremia in other countries in the literature. The data revealed the average annual incidences of bacteremia due to Aeromonas, Vibrio, and Salmonella species were 76, 38, and 103 cases/million inhabitants, respectively. The incidence of Aeromonas bacteremia was higher than those in Western countries.

Antimicrobial susceptibility of pathogens isolated from patients with complicated intra-abdominal infections at five medical centers in Taiwan that continuously participated in the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2006 to 2010

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance program designed to longitudinally monitor the in vitro activity of antimicrobial agents against pathogens that cause intra-abdominal infections (IAIs). In this study, trends in antimicrobial resistance during the period 2006 to 2010 were analyzed at five tertiary-care hospitals in Taiwan. Enterobacteriaceae accounted for the majority (80.9%) of the 2417 Gram-negative isolates, and the two most common species were Escherichia coli (38.8%) and Klebsiella pneumoniae (23.5%). The rates of susceptibility of Enterobacteriaceae isolates to cephalosporins decreased during the study period. Although carbapenems, fluoroquinolones, piperacillin-tazobactam, and amikacin were active in vitro against more than 80% of the Enterobacteriaceae isolates, the activity of carbapenems declined during the study period. Extended-spectrum β-lactamase (ESBL) production in E. coli was steady, but that in K. pneumoniae decreased during the study period. The rate of ESBL-producing species was three-fold higher among patients with nosocomial IAIs than among patients with community-acquired IAIs. The majority of isolates from liver were K. pneumoniae (69%) and very few of those isolates were ESBL producers (0.9%). Pseudomonas aeruginosa (9.3%) and Acinetobacter baumannii (3.8%) were the two most common non-Enterobacteriaceae. P. aeruginosa showed improved susceptibility, whereas A. baumannii showed a rapid development of resistance during the study period. There was marked geographic variation in resistance patterns of the isolates obtained during the study period. Northern Taiwan had the highest rate of ESBL producers and the highest rate of ceftazidime resistance among P. aeruginosa isolates. Central Taiwan had the lowest rate of ESBL producers but the highest rates of carbapenem resistance among P. aeruginosa and A. baumannii isolates. Continuous monitoring and regular updates of epidemiological data are needed to guide appropriate empiric antimicrobial therapy.