Characterization of Pharmacogenetic Information in Food and Drug Administration Drug Labeling and the Table of Pharmacogenetic Associations.

BACKGROUND: The US Food and Drug Administration (FDA) recommends using only FDA-reviewed pharmacogenetic information to make prescribing decisions based on genetic test results. Such information is available in drug labeling and in the Table of Pharmacogenetic Associations ("Associations table"). OBJECTIVE: To compile a list of drug-gene pairs from drug labeling and the Associations table and categorize the pharmacogenetic information and clinical outcome associated with each drug-gene pair. METHODS: This was a cross-sectional analysis of pharmacogenetic information in the Associations table and individual drug labeling in March 2020. We used the Table of Pharmacogenomic Biomarkers in Drug Labeling to identify drug labels to review. We categorized the pharmacogenetic information for each drug-gene pair according to whether the purpose was to describe (1) polymorphisms affecting drug disposition (metabolism or transport), (2) polymorphisms affecting a direct drug target, (3) variants associated with adverse drug reaction (ADR) susceptibility, (4) variants associated with therapeutic failure, (5) a biomarker-defined indication, or (6) a biomarker-defined ADR. We also categorized the clinical outcome-efficacy, safety, or unknown-associated with each drug-gene pair. We reported counts and proportions of drug-gene pairs in each pharmacogenetic information and clinical outcome category. RESULTS: We identified 308 drug-gene pairs, of which 36% were associated with a biomarker-defined drug indication, 33% with polymorphic drug metabolism, and 28% with ADR susceptibility. Most drug-gene pairs (n = 267, 87%) were associated with an efficacy or safety-related outcome. CONCLUSION AND RELEVANCE: FDA-reviewed pharmacogenetic information is available for more than 300 drug-gene pairs and can help guide prescribing decisions.

Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands.

In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.

Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study.

Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥ 4 µg/ml) was 4.6% and penicillin resistance (MIC, ≥ 8 µg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.

High prevalence of multidrug-resistant nonfermenters in hospital-acquired pneumonia in Asia.

RATIONALE: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remain important causes of morbidity and mortality. Increasing antimicrobial resistance has aroused the concern of the failure of antibiotic treatment. OBJECTIVES: To determine the distribution of the bacterial isolates of HAP and VAP, their antimicrobial resistance patterns, and impact of discordant antibiotic therapy on clinical outcome in Asian countries METHODS: A prospective surveillance study was conducted in 73 hospitals in 10 Asian countries from 2008-2009. A total of 2,554 cases with HAP or VAP in adults were enrolled and 2,445 bacterial isolates were collected from 1,897 cases. Clinical characteristics and antimicrobial resistance profiles were analyzed. MEASUREMENT AND MAIN RESULTS: Major bacterial isolates from HAP and VAP cases in Asian countries were Acinetobacter spp., Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae. Imipenem resistance rates of Acinetobacter and P. aeruginosa were 67.3% and 27.2%, respectively. Multidrug-resistant rates were 82% and 42.8%, and extensively drug-resistant rates were 51.1% and 4.9%. Multidrug-resistant rate of K. pneumoniae was 44.7%. Oxacillin resistance rate of S. aureus was 82.1%. All-cause mortality rate was 38.9%. Discordant initial empirical antimicrobial therapy increased the likelihood of pneumonia-related mortality (odds ratio, 1.542; 95% confidence interval, 1.127-2.110). CONCLUSIONS: Acinetobacter spp., P. aeruginosa, S. aureus, and K. pneumoniae are the most frequent isolates from adults with HAP or VAP in Asian countries. These isolates are highly resistant to major antimicrobial agents, which could limit the therapeutic options in the clinical practice. Discordant initial empirical antimicrobial therapy significantly increases the likelihood of pneumonia-related mortality.

Spread of methicillin-resistant Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS: We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS: MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS: Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.

Significance of the myxovirus resistance A (MxA) gene -123C>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection.

Myxovirus resistance A (MxA) is an antiviral protein induced by interferon alpha and beta (IFN-alpha, IFN-beta) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-alpha and IFN-beta treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-beta-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-beta stimulation. Endogenous IFN-alpha and IFN-beta induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minor-allele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-alpha and IFN-beta induction such as SARS coronavirus.

High rate of reduced susceptibility to ciprofloxacin and ceftriaxone among nontyphoid Salmonella clinical isolates in Asia.

This multinational study from Asia revealed that reduced susceptibility to ciprofloxacin (MIC, 0.125 to 1 microg/ml) in nontyphoid Salmonella isolates was common in Taiwan (48.1%) and Thailand (46.2%) and in S. enterica serotype Choleraesuis (68.8%) and S. Virchow (75.0%) from all countries. Reduced susceptibility to ceftriaxone (MIC, 2 to 8 microg/ml) remained uncommon in Asia, except in Taiwan (38.0%) or in S. Typhimurium (25.0%) from all countries.

Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b.

BACKGROUND & AIMS: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) alpha-2b alone or in combination with lamivudine. METHODS: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN alpha-2b (100 mug/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 +/- 0.8 years). RESULTS: Of 266 patients enrolled in the initial study, 172 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A-infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P < .001). CONCLUSIONS: HBeAg loss after treatment with PEG-IFN alpha-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A-infected patients. Therefore, PEG-IFN alpha-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy.

Economic evaluation of universal infant vaccination with 7vPCV in Hong Kong.

OBJECTIVES: The purpose of this study was to evaluate the clinical and economic benefits of routine infant vaccination with seven-valent pneumococcal conjugate vaccine (7vPCV) in Hong Kong. METHODS: A decision-analytic model was populated with local age-specific incidence data to simulate the expected health outcomes resulting from 7vPCV vaccination of a birth cohort of 57,100 children compared with an unvaccinated cohort over a 10-year horizon. Primary analyses were conducted from a payer perspective, using local inpatient and outpatient costs associated with the treatment of pneumococcal disease. Vaccine efficacy rates were consistent with results from pivotal clinical trials. The reduction in adult invasive pneumococcal disease (IPD) and associated cost avoidance due to the indirect effect of vaccination were estimated in line with published overseas rates. RESULTS: Universal 7vPCV vaccination was estimated to prevent 524 cases of IPD and more than 2580 cases of otitis media in the birth cohort over a 10-year period, leading to a reduction of HK$28.7 million (US$3.7 million) in direct medical costs. Additional cost savings from the indirect prevention of 919 adult cases of IPD during this time period also resulted. Overall, 7vPCV vaccination was estimated to have an incremental cost per life-year gained of HK$50,456 (US$6460) from a payer perspective or HK$46,308 (US$5929) when both direct and indirect costs were included. CONCLUSION: With reference to the World Health Organization's threshold for cost-effectiveness, results from this study indicate that routine infant vaccination with 7vPCV is a cost-effective intervention because of the added cost savings resulting from the indirect effect of vaccination on adult disease.

Health-related quality of life of Southern Chinese with chronic hepatitis B infection.

BACKGROUND: Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection. AIM: To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL. METHODS: 520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC) were interviewed with a structured questionnaire, the SF-36 Health Survey version 2 (SF-36v2), and the Chronic Liver Disease Questionnaire (CLDQ). The differences in SF-6D health preference values and SF-36v2 scores between each CHB group and Hong Kong population norms were assessed by t-test. ANOVA was used to compare the mean SF-6D health preference, SF-36v2 scores, and CLDQ scores among CHB groups. Multiple linear regressions were performed to identify determinants of HRQOL. RESULTS: CHB patients had significantly lower SF-36v2 scores than the population norm. The SF-6D values of CHB patients with uncomplicated disease, impaired liver function, HCC and cirrhosis were 0.755, 0.745, 0.720 and 0.701, respectively, all significantly lower than the population norm of 0.787. Advanced stage of CHB illness, anti-viral treatment, bilirubin level, psychological co-morbidity, younger age and female were associated with poorer HRQOL. CONCLUSION: CHB infection had a negative impact on HRQOL. There was a progressive decrease in health preference values with CHB disease progression. The results can be used for the estimation of quality adjusted life years (QALYs) for CHB patients in cost effectiveness or cost utility studies. TRIAL REGISTRATION: http://www.hkclinicaltrials.com; HKCTR-151.

Utility of clinical features with fine needle aspiration biopsy for diagnosis of Warthin tumor.

BACKGROUND: Conservative management of Warthin tumor (WT) may be a viable alternative to surgery, but there are concerns of missed malignancies on fine needle aspiration biopsy (FNAB). The purpose of this study is to measure the sensitivity and positive predictive value of FNAB for WT, and to identify clinical features associated with WT that can aid in this diagnosis. METHODS: Retrospective analysis of patients from January 1, 2006 to April 30, 2017 at a tertiary care center in London, Ontario, Canada. All patients with a diagnosis of WT on FNAB or resection were included. Electronic medical records were identified for 177 patients that fit the criteria. Study outcomes included the sensitivity and positive predictive value of FNAB alone for WT, and, when including clinical features associated with WT. RESULTS: The mean age of patients in this study was 63.2 years (SD 10.4); 115 (65%) were male, and 157 (89%) were past or present smokers. The measured sensitivity and positive predictive value of FNAB for WT were 95.8 and 97.2% respectively. Two cases were classified as WT on FNAB but confirmed at resection as mucoepidermoid carcinoma and acinic cell carcinoma. When only patients with multifocal, bilateral or incidental tumors were assessed, sensitivities and positive predictive values for each were 100%. Isolating for inferior pole location also resulted in a positive predictive value of 100%. CONCLUSIONS: The sensitivity and positive predictive value of FNAB for WT in this study are high, with two false negatives on FNAB. Multifocal, bilateral, incidentaloma and inferior pole location were identified as potential clinical features that may increase the diagnostic confidence for WT, strengthening the argument for conservative management in these patients. Overall, this study serves as an initial exploration into whether clinical features may be included with FNAB results to improve the sensitivity and positive predictive value of diagnosing WT. Further research is necessary before these findings can be translated into clinical practice.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens.

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate>30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P<0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

Antimicrobial susceptibility of Shigella isolates in eight Asian countries, 2001-2004.

BACKGROUND AND PURPOSE: Shigellosis is a major health problem in developing countries, causing 91 million episodes and 414,000 deaths in Asia annually. Because of increasing trends towards drug resistance, this study was undertaken to monitor local resistance patterns of Shigella isolates from 8 Asian countries. METHODS: Ninety eight Shigella isolates collected from 8 centers in 8 Asian countries from July 2001 to July 2004 were analyzed in terms of serogroup distribution and antimicrobial susceptibility. RESULTS: The most common serogroup of Shigella isolates was Shigella flexneri (49/98, 50%), followed by Shigella sonnei (44/98, 45%). The highest resistance rate was found for trimethoprim-sulfamethoxazole (81%), followed by tetracycline (74%) and ampicillin (53%). Overall, 76 Shigella isolates (78%) were multidrug-resistant strains; S. flexneri had a higher multidrug resistance rate than S. sonnei (74% vs 23%). Increasing ciprofloxacin and ceftriaxone resistance was observed; approximately 10% and 5% of isolates were resistant to ciprofloxacin and ceftriaxone, respectively. Five ceftriaxone-non-susceptible strains (from Taiwan [3], Hong Kong [1] and The Philippines [1]) and 10 ciprofloxacin-non-susceptible strains (from Hong Kong [2], The Philippines [1], Korea [2], Vietnam [4] and Sri Lanka [1]) were isolated. CONCLUSIONS: High rates of multidrug resistance and steady increases in ceftriaxone and ciprofloxacin resistance of Shigella are serious pubic health concerns in Asian countries. Continuous monitoring of resistance patterns among Shigella isolates is necessary.

Antimicrobial stewardship for acute-care hospitals: An Asian perspective.

Inappropriate use of antibiotics is contributing to a serious antimicrobial resistance problem in Asian hospitals. Despite resource constraints in the region, all Asian hospitals should implement antimicrobial stewardship (AMS) programs to optimize antibiotic treatment, improve patient outcomes, and minimize antimicrobial resistance. This document describes a consensus statement from a panel of regional experts to help multidisciplinary AMS teams design programs that suit the needs and resources of their hospitals. In general, AMS teams must decide on appropriate interventions (eg, prospective audit and/or formulary restriction) for their hospital, focusing on the most misused antibiotics and problematic multidrug-resistant organisms. This focus is likely to include carbapenem use with the goal to reduce carbapenem-resistant gram-negative bacteria. Rather than initially trying to introduce a comprehensive, hospital-wide AMS program, it would be practical to begin by pilot testing a simple program based on 1 achievable core intervention for the hospital. AMS team members must work together to determine the most suitable AMS interventions to implement in their hospitals and how best to put them into practice. Continuous monitoring and feedback of outcomes to the AMS teams, hospital administration, and prescribers will enhance sustainability of the AMS programs.

Emergence and Dissemination of ST131 Escherichia coli Isolates Among Patients with Hospital-Acquired Pneumonia in Asian Countries.

We investigated the molecular epidemiology and microbiological characteristics of 51 Escherichia coli isolates causing hospital-acquired pneumonia (HAP) in eight Asian areas. Sequence type 131 (ST131) was the most prevalent among E. coli isolates causing HAP, especially in South Korea, Thailand, and the Philippines. The current study showed that CTX-M-15-producing E. coli ST131 has emerged in and disseminated among patients with HAP in Asia. Our data suggest that this pandemic clone poses an important public health threat even in nosocomial infections.

Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.

BACKGROUND: Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. METHODS: 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. FINDINGS: 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). INTERPRETATION: Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.

In vitro activity of Tedizolid phosphate against multidrug-resistant Streptococcus pneumoniae isolates from Asian countries.

Tedizolid phosphate is a second-generation oxazolidinone prodrug that is potential activity against a wide range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant streptococci, and vancomycin-resistant enterococci. The in vitro activity of tedizolid and other comparator agents against multidrug-resistant (MDR) pneumococci from various Asian countries were evaluated. Of the S. pneumoniae clinical pneumonia isolates collected during 2008 and 2009 from 8 Asian countries (Korea, Taiwan, Thailand, Hong Kong, Vietnam, Malaysia, Philippines, and Sri Lanka), 104 isolates of MDR pneumococci were included in this study. Antimicrobial susceptibility testing for 18 antimicrobial agents was performed by broth microdilution method. Tedizolid was highly active against pneumococci. All isolates tested were inhibited at a tedizolid minimum inhibitory concentration (MIC) value of ≤0.25µg/ml (ranged from ≤0.03µg/ml to 0.25µg/ml). The MIC50 and MIC90 of tedizolid against MDR pneumococci were both 0.12µg/ml, while MIC50 and MIC90 of linezolid were 0.5µg/ml and 1µg/ml, respectively. In addition, tedizolid maintained the activity against S. pneumoniae regardless of the extensively drug-resistant (XDR) phenotype of the isolates. The activity of tedizolid was excellent against all types of MDR pneumococci, exhibiting and maintaining at least 4-fold-greater potency compared to linezolid, regardless of resistance phenotypes to other commonly utilized agents. Tedizolid has the potential to be an agent to treat infections caused by MDR pneumococci in the Asia.

Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in asian countries: a study by the Asian Network for Surveillance of Resistant Pathogens.

To evaluate the clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries, we performed a prospective observational study of 233 cases of adult pneumococcal pneumonia in 9 Asian countries from January 2000 to June 2001. Among 233 isolates, 128 (55%) were not susceptible to penicillin (25.3% were intermediately susceptible, and 29.6% were resistant). Clinical severity of pneumococcal pneumonia was not significantly different between antibiotic-resistant and antibiotic-susceptible groups. Mortality rates among patients with pneumococcal pneumonia caused by penicillin-, cephalosporin-, or macrolide-resistant strains were not higher than those with antibiotic-susceptible pneumococcal pneumonia. Bacteremia and mechanical ventilation were significant risk factors for death, but any kind of antibiotic resistance was not associated with increased mortality due to pneumococcal pneumonia. Outcome of pneumococcal pneumonia was not significantly affected by drug resistance, and current antimicrobial regimens are mostly effective in the treatment of pneumococcal pneumonia, despite the widespread emergence of in vitro resistance.

Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.

The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that "putative serotype 6E" is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.

Risk factors and pathogenic significance of bacteremic pneumonia in adult patients with community-acquired pneumococcal pneumonia.

OBJECTIVE: This study was performed to identify risk factors for the development of bacteremic pneumonia and to evaluate the impact of bacteremia on the outcome of pneumococcal pneumonia. METHODS: Using a database from a surveillance study of community-acquired pneumococcal pneumonia, we compared data of the bacteremic group with that of the non-bacteremic group. RESULTS: Among 981 adult patients with pneumococcal pneumonia, 114 (11.6%) patients who had documented pneumococcal bacteremia were classified into the bacteremic group. In a multivariable analysis, use of immunosuppressant drugs, younger age (<65 years), and DM were independent risk factors associated with the development of bacteremic pneumonia among patients with pneumococcal pneumonia (all P < 0.05). The mortality rate was significantly higher in the bacteremic group than in the non-bacteremic group (28.6% vs. 8.5%; P < 0.001). The multivariable analysis revealed that concomitant bacteremia was one of the significant risk factors associated with mortality (OR, 2.57; 95% CI, 1.24-5.29), along with cerebrovascular disease and presentation with septic shock (all P < 0.05). CONCLUSIONS: Bacteremia was a common finding in pneumococcal pneumonia and was associated with a higher mortality rate. Several clinical variables may be useful for predicting bacteremic pneumonia among patients with pneumococcal pneumonia.