Yonghong Yang

High Prevalence of Antimicrobial Resistance among Clinical Streptococcus pneumoniae Isolates in Asia (an ANSORP Study)

ABSTRACT A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs ≥ 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC90s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC90s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan19F clone and the Spain23F clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.

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.

Changing Trends in Antimicrobial Resistance and Serotypes of Streptococcus pneumoniae Isolates in Asian Countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

ABSTRACT 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.

Evaluation of Binax NOW, an Assay for the Detection of Pneumococcal Antigen in Urine Samples, Performed among Pediatric Patients

In our evaluation of a new assay for the detection of pneumococcal antigen in urine (Binax NOW; Binax), the test result was no more likely to be positive among 88 children with radiographically confirmed pneumonia than among 198 control subjects; however, it was significantly more likely to be positive among children who were nasopharyngeal carriers of pneumococci. This test is not likely to be useful for distinguishing children with pneumococcal pneumonia from those who are merely colonized.

Carriage of Antibiotic-Resistant Pneumococci among Asian Children: A Multinational Surveillance by the Asian Network for Surveillance of Resistant Pathogens (ANSORP)

To investigate the nasal carriage of antibiotic-resistant pneumococci by children, anterior nasal swabs were done for 4963 children <5 years old in 11 countries in Asia and the Middle East. In total, 1105 pneumococci isolates (carriage rate, 22.3%) were collected, 35.8% of which were found to be nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and Vietnam (70.4%). Penicillin resistance was related to residence in urban areas, enrollment in day care, and a history of otitis media. The most common serogroups were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to strains of invasive isolates from adult patients. Data in this study documented the high rate of penicillin or multidrug resistance among isolates of pneumococci carried nasally in children in Asia and the Middle East and showed that this is due to the spread of a few predominant clones in the region.

The Remaining Challenge of Pneumonia The Leading Killer of Children

Despite a drop in overall child mortality cases since 2000, pneumonia still killed nearly 1.6 million children less than 5 years of age this year, and it remains the leading cause of death in this age group—more than AIDS, malaria, and measles combined. In developing countries, the disease burden among children is particularly high, because implementation of life-saving interventions such as vaccination, exclusive breast-feeding during the first 6 months of life, good nutrition for older children, handwashing, and reducing indoor air pollution from cook stovesand tobacco smoke, continues to be limited. Two of the most common pneumonia-causing pathogens, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae, can be prevented through vaccination. Previous Hib vaccination efforts in developing countries have shown dramatic reductions in disease burden. A large 1997 trial in the Gambia demonstrated vaccine efficacy of 95% against invasive Hib disease. In the same Gambia study, efficacy of the (9-valent) vaccine was 77% against pneumococcal disease caused by the serotypes targeted by the vaccine and 37% against all types of severe pneumonia which are often fatal. Yet, despite these findings and recommendations from the World Health Organization (WHO) that both Hib and PCVs be included in routine infant immunization programs in all countries, many developing countries have yet to adopt these life-saving interventions. Of the 2008 global cohort of 129 million (surviving) newborn children, 93 million (71% of all born) were not immunized with Hib vaccines and 121 million (93% of all born) were not immunized with PCVs. Vaccine cost remains a major deterrent in vaccine adoption as well as concern over the fact that an earlier version—the 7-valent PCV—did not cover key serotypes found in low-income settings, but the stage has been set for a revolution in pneumococcal vaccine delivery and access. Financing is now available for low-income countries to introduce life-saving vaccines that have, until now, been out of reach for overstretched developing country health budgets. In June 2009, the governments of Italy, the United Kingdom, Canada, the Russian Federation, and Norway, and the Bill and Melinda Gates Foundation launched the pilot pneumococcal Advance Market Commitment (AMC)—an innovative financing mechanism designed to stimulate the development, manufacture, and uptake of affordable vaccines that meet the needs of developing countries—with a collective US

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.

1.5 billion commitment. In addition, the Global Alliance for Vaccine and Immunization will help fund the total cost of these vaccines by contributing up to US

Antimicrobial susceptibility of Haemophilus influenzae among children in Beijing, China, 1999–2000

1.3 billion between 2010 and 2015. Acting on the Gates Foundation’s call to make this the “decade of vaccines,” in March of this year, GlaxoSmithKline and Pfizer Inc, the 2 makers of the new 10and 13-valent PCVs (PCV10 and PCV13), confirmed their commitment by signing an agreement to become the first companies to supply pneumococcal vaccines through the AMC. Two other companies with products in development have also signed on. This means that the newest pneumococcal vaccines will be available for developing countries, where they are urgently needed, and at a fraction of the price charged in industrialized countries. New vaccines available through the AMC stand to protect against more strains of pneumococcal disease prevalent in the developing world. Although serotypes included in PCV7 covered 65% to 80% of serotypes associated with invasive pneumococcal disease in western industrialized countries, the coverage varied in developing countries and was anticipated to be lower. This left leaders outside of the western industrialized world hesitant to invest in PCV7, despite the urging of the World Health Organization. Many countries decided to hold their decisions to implement pneumococcal vaccines until newer vaccines with broader coverage were available. The time has come for all countries to act. In addition to the “older” vaccines such as Hib vaccine and PCV7, the new generation vaccines—PCV10 and PCV 13—are available now and expected to cover 50% to 80% of invasive pneumococcal disease not just in industrialized countries, but worldwide. In addition to the PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV10 covers against strains 1, 5, and 7F, while PCV13 also includes serotypes 1, 3, 5, 6A, 7F, and 19A, offering broader coverage against strains prevalent throughout Africa and Asia. As we mark the second World Pneumonia Day, developing countries must seize the moment to eliminate the leading causes of pneumonia in the world. As pediatricians and researchers, we can Accepted for publication September 7, 2010. From the *The Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; †Division of Maternal and Child Health, Aga Khan University, Karachi, Pakistan; ‡Sabin Vaccine Institute, Washington, DC; §European Society of Clinical Microbiology and Infectious Diseases, Barcelona, Spain; ¶William H. Foege Chair in Global Health, Rollins School of Public Health, Emory University, Atlanta, GA; Division of Infectious Disease, Jordan University Hospital, Amman, Jordan; **International Vaccine Access Center, Johns Hopkins University, Baltimore, MD; ††Department of Microbiology, Bangladesh Institute of Child Health, Dhaka Shishu Hospital, Dhaka, Bangladesh; ‡‡Center for Vaccine Development, Bamako, Mali; §§Kenya Paediatric Association, Nairobi, Kenya; and ¶¶Pediatrics, Beijing Children’s Hospital, Beijing, China. Supported by Sabin Vaccine Institute, Pneumococcal Awareness Council of Experts. Address for correspondence: Ron Dagan, MD, Pediatric Infectious Disease Unit, Soroka University Medical Center, POB 15, Beer-Sheva 84101 Israel. E-mail: rdagan@bgu.ac.il. Copyright

Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae from Asian Countries: ANSORP Study

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.

Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs

A study on the nasopharyngeal carriage and antimicrobial susceptibility of Haemophilus influenza among children was conducted in Beijing Childrens Hospital from April to May 2000. The study included 292 children between 1 and 60 mo of age with acute upper respiratory tract infection. Nasopharyngeal swabs from these patients were cultured, and 105 Haemophilus influenzae strains were isolated, 3 of which were type b. Antibiotic susceptibility of the strains was determined using disk diffusion and E‐tests and the results compared with those of isolates from children with pneumonia in 1999. The carriage rate of Haemophilus influenzae was 36.0% (105/292). It was found that 4.8% and 1.0% of isolates were resistant to ampicillin and cefaclor, respectively, and 5.7%, 16.2% and 77.1% were resistant to chloramphenicol, tetracycline, and sulphamethoxazole/trimethoprim, respectively. Amoxicillin/clavulanic acid, cefuroxime, ceftriaxone, azithromycin, and clarithromycin were uniformly active to all strains. Compared with the data from 1999, there was a significant increase in resistance to tetracycline (from 12.7% in 1999 to 16.2%) and sulphamethoxazole/trimethoprim (from 40.5% in 1999 to 77.1%).