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.

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.

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.

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.

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.

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.

Clinical impact of methicillin resistance on outcome of patients with Staphylococcus aureus infection: a stratified analysis according to underlying diseases and sites of infection in a large prospective cohort.

OBJECTIVE: This study was conducted to identify the predictors of mortality and to evaluate the impact of methicillin resistance on outcome in patients with Staphylococcus aureus infection according to underlying conditions and type of infection. METHODS: An observational cohort study including 4949 patients with S. aureus infection was conducted. We compared data from patients with MRSA infection with those with MSSA infection. RESULTS: The 30-day mortality rate of MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P < 0.001). However, MRSA infection was not found to be independent risk factor for mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80-1.32). When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was found to be significantly associated with mortality in multivariate analysis (Adjusted OR = 1.69, 95% CI = 1.15-2.49). When the 30-day mortality rates were compared according to underlying diseases, the 30-day mortality rate of MRSA group was significantly higher than that of MSSA group in patients with malignancy or renal diseases. MRSA infection was also found to be one of the independent risk factors for mortality in patients with malignancy (adjusted OR = 1.69, 95% CI = 1.06-2.70) and in those with renal disease (adjusted OR = 1.70, 95% CI = 1.0-2.89), after adjustment for host variables. CONCLUSIONS: Methicillin resistance adversely affected the outcome of patients with S. aureus infection, in patients with cancer or renal disease and in those with S. aureus bacteremia, although MRSA infection was not found to be significantly associated with higher mortality in overall patient population.

CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese.

CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) -336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)-coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the -336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the -336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 -336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating.