Cheng-Hsun Chiu

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 Drug-Resistant Streptococcus pneumoniae in Asian Countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.

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.

Salmonella enterica Serotype Choleraesuis: Epidemiology, Pathogenesis, Clinical Disease, and Treatment

SUMMARY Nontyphoid Salmonella strains are important causes of reportable food-borne infection. Among more than 2,000 serotypes, Salmonella enterica serotype Choleraesuis shows the highest predilection to cause systemic infections in humans. The most feared complication of serotype Cholearesuis bacteremia in adults is the development of mycotic aneurysm, which previously was almost uniformally fatal. The advances in diagnostic techniques, surgical care, and antimicrobial therapy have greatly improved the survival of these patients. However, the recent emergence of serotype Choleraesuis that is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and, notably, fluoroquinolone antibiotics has aroused concern about the use of these agents for the empirical treatment of systemic infection caused by this organism. In view of the serious implications of the situation, the chain of transmission and mechanism of resistance should be carefully studied to reduce the spread of infection and threat to human health. To date, there are no vaccines available to prevent serotype Choleraesuis infections in humans. The availability, in the near future, of the genome sequence of serotype Cholearesuis will facilitate the development of effective vaccines as well as the discovery of new targets for novel antimicrobial agents.

Antimicrobial Resistance in Nontyphoid Salmonella Serotypes: A Global Challenge

Increasing antimicrobial resistance in nontyphoid Salmonella species has been a serious problem for public health worldwide. The high rate of resistance is hampering the use of conventional antibiotics, and growing resistance to newer antimicrobial agents is aggravating the situation. The circumstances of occurrence and spread of antimicrobial resistance are complex; however, a major cause is the widespread use of antimicrobial agents in food animals, particularly in animal feed. Genetic analysis has indicated that the source of resistance is frequently a transferable plasmid. Recent studies have revealed that some serotype-specific virulence plasmids form hybrid plasmids through recombination with resistance plasmids or acquire gene cassettes consisting of multiple resistance genes. Such evolutionary events provide a virulent strain the advantage of survival in an unfavorable drug environment. In view of the serious implications associated with drug-resistant Salmonella species, a more deliberate use of antibiotics in both human medicine and animal industry is warranted. Continued surveillance of antimicrobial resistance and use of antimicrobial agents in food animals is also indispensable.

The 1998 Enterovirus 71 Outbreak in Taiwan: Pathogenesis and Management

The most recently discovered enterovirus, enterovirus 71 (EV71), is neurotropic and may cause severe disease and sudden death in children. In 1998, a large outbreak of enterovirus infection occurred in Taiwan that resulted in 405 severe cases in children and 78 deaths. Of the 78 children who died, 71 (91%) were <5 years old. EV71 was the primary agent in fatal cases of infection. Most of these patients died within 1-2 days of admission to the hospital. We hypothesize that EV71 directly attacks the central nervous system and causes neurogenic pulmonary edema and cardiac decompensation through the mechanism of sympathetic hyperactivity and inflammatory responses. Early recognition of risk factors and intensive care are crucial to successful treatment of this fulminant infection. After poliovirus is eradicated, EV71 will become the most important enterovirus that affects children, and development of a vaccine may be the only effective measure against it.

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy

Aim: The mechanism of pulmonary oedema, a life‐threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71‐related pulmonary oedema. Methods: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme‐linked immunosorbent assay. Results: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin‐6 (IL‐6) (947 ± 1239 vs 4.9 ± 3.1 pg/ml, p= 0.0003), tumour necrosis factor‐α (TNF‐α) (22.4 ± 29.5 vs 5.3 ± 1.0 pg/ml, p= 0.0035), interleukin 1β (IL‐1β) (48.4 ± 85.2 vs 4.9 ± 10.1 pg/ml, p= 0.01), white blood cell count (28.3 ± 7.6 vs 15.5 ± 6.8 109/L, p± 0.0001) and blood glucose (501 ± 186 vs 165 ± 117 mg/dL, p= 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL‐6 < 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%.

Norovirus infection as a cause of diarrhea-associated benign infantile seizures.

BACKGROUND Norovirus and rotavirus cause outbreaks of diarrheal disease worldwide. This prospective observational study was undertaken to investigate the clinical characteristics and complications, with a focus on convulsive disorders, of gastroenteritis caused by norovirus and rotavirus in hospitalized pediatric patients in northern Taiwan. METHODS Children hospitalized with acute gastroenteritis in Chang Gung Childrens Hospital from August 2004 through January 2007 were enrolled in the study. Rotavirus and norovirus were detected by reverse-transcriptase polymerase chain reaction with fecal specimens and were genotyped by sequence analysis. The symptoms and complications, in particular convulsions, of acute gastroenteritis caused by rotavirus and norovirus were reviewed and compared. The occurrence of convulsions associated with norovirus infection was specifically analyzed and discussed. The neurological outcomes for all norovirus-infected patients with or without convulsions were followed up for 1 year. Results. Among the 353 patients with acute viral gastroenteritis without coinfection, rotavirus and norovirus isolates were detected in 101 patients (28.6%) and 64 patients (18.1%), respectively. We compared the symptoms between the 2 groups and found that rotavirus caused a higher frequency and longer duration of vomiting and a higher body temperature than did norovirus. Norovirus infection, on the other hand, caused significantly longer hospital stays (mean duration of stay [interquartile range], 6 [5-8] days vs. 5 [4-7] days; P <.001) and a significantly higher incidence of convulsions than did rotavirus infection (29.7% vs. 5%; P <.001). Three of the 19 patients with convulsions showed an abnormal record on electroencephalogram, but none had any neurological sequelae at the subsequent 1-year follow-up. The majority of norovirus strains (41 of the 56 genotypeable strains) belonged to genogroup GGII/4. Conclusions. Norovirus is a major cause of acute gastroenteritis in children. This study identified norovirus as an emerging agent causing convulsive disorder in children, particularly in young infants. Long-term neurological sequelae are uncommon.

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.

National survey of invasive pneumococcal diseases in Taiwan under partial PCV7 vaccination in 2007: emergence of serotype 19A with high invasive potential.

We conducted an active, population-based laboratory surveillance study to evaluate the epidemiologic features of invasive pneumococcal disease (IPD) in Taiwan. Concurrently, nasopharyngeal colonization of Streptococcus pneumoniae was evaluated among 1128 healthy children aged <or=5 years. The overall incidence was highest among children aged 2-4 years (15.6/100,000). Serotype 19A, which had never been reported in Taiwan previously, caused a substantial fraction of the invasive diseases (OR, 9.6; 95% CI, 3.1-29.4) among children aged 2-4 years. Comparing serotype distributions of the isolates from nasopharyngeal colonization among children aged <or=5 years, serotypes 14 (OR, 17.3; 95% CI, 5.2-57.9) and 19A (OR, 14.9; 95% CI, 1.9-117) had the highest invasive potential. The study found that serotype 19A expanded in Taiwan, a country with a low 7-valent conjugate pneumococcal vaccine coverage. The 7-valent conjugate pneumococcal vaccines covered 73% of cases in children aged between 2 and 4 years, and 64.7% of cases in children aged <2 years. Among patients aged >or=65 years, the 23-valent pneumococcal polysaccharide vaccine covered 70.4% of cases. In the future, a broader pneumococcal vaccine is needed.