Thomsen-Friedenreich antigen activation as a predictor for clinical outcome of pediatric patients with invasive pneumococcal disease.

BACKGROUND: The most severe form of pneumococcal disease is invasive pneumococcal disease (IPD), including empyema, sepsis and meningitis. Thomsen-Friedenreich antigen (TA; Galß1-3GalNAc) activation is known to be a predictor of Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS). There have been limited data to correlate TA activation and overall disease severity of IPD in children. The study aimed to prove the positive correlation between TA activation and disease severity and to demonstrate the trend of TA level during the disease course. METHODS: We retrospectively reviewed the medical records from 38 pediatric patients aged from 0 to 18 years with microbiologically-confirmed IPD between 2010 and 2015 at a medical center in Taiwan. All cases underwent TA activation testing by the fluorescence-labeled peanut lectin agglutination method. Medical information including demographic data, laboratory findings, co-morbidities, and outcome was collected and reviewed. We compared the clinical manifestations and associated co-morbidities between TA-positive and TA-negative patients. RESULTS: Among the 38 patients, 25 (66%) showed TA activation. Compared to TA-negative patients, patients with TA activation had a statistically higher rate of prolonged anemia, thrombocytopenia, and acute kidney injury. TA-positive patients also had a longer intensive care unit stay and overall hospitalization days. The TA levels usually peaked 5-10 days after disease onset. Twenty-one pneumococcal isolates were recovered from the patients and serotyping was determined in 11 isolates: 10 serotype 19A and 1 serotype 3. CONCLUSIONS: TA determination not only helps to diagnose Sp-HUS but also is a predictor for IPD severity. Among hospitalized patients with severe pneumococcal disease, the peak of TA level usually appeared 5-10 days after disease onset.

Non-typeable Streptococcus pneumoniae infection in a medical center in Taiwan after wide use of pneumococcal conjugate vaccine.

BACKGROUND: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. METHODS: Clinical isolates of S.pneumoniae from January 2012 to December 2015 at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. RESULTS: During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p = 0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. CONCLUSIONS: A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone.

Fluoroquinolone-nonsusceptible Streptococcus pneumoniae isolates from a medical center in the pneumococcal conjugate vaccine era.

BACKGROUND/PURPOSE: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Resistance to fluoroquinolones (FQ) is associated with clinical failure when treating pneumococcal diseases and increase of mortality. METHODS: We collected clinical isolates of S. pneumoniae from January 2011 to July 2015 at Chang Gung Memorial Hospital, Taoyuan, Taiwan. Susceptibility to FQ was examined by disk diffusion method. Levofloxacin or moxifloxacin-nonsusceptible S. pneumoniae isolates were analyzed by serotyping, multilocus sequence typing, and sequencing of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE. RESULTS: During the study period, 42 FQ-nonsusceptible pneumococcal isolates were identified. The rate increased from 1.6% of total pneumococcal isolates (2 of 127) in 2011 to 4.6% (13 of 283) in 2014, then decreased to 1.5% (3 of 202) in the first half of 2015. These isolates belonged to 13 serotypes, and serotype 14 (12 of 42, 33.3%) was the most prevalent. Most of the isolates belonged to international clones or their variants. After QRDR analysis, there were 19 isolates in five clusters that shared both the same sequence type and QRDR mutation. CONCLUSIONS: FQ resistance initially emerged in either vaccine or nonvaccine serotypes. The majority of isolates were international clones or related variants, suggesting that resistance was disseminated through clonal spread. The wide use of pneumococcal conjugate vaccine since 2013 appears to have reduced the spread of FQ-nonsusceptible pneumococci.

Epidemiology of culture-confirmed infections of Streptococcus pneumoniae (2012-2015) and nasopharyngeal carriage in children and households in Taiwan (2014-2015).

PURPOSE: An observational study was performed to investigate the carriage rate and serotypes of Streptococcus pneumoniae in the 13-valent pneumococcal conjugate vaccine (PCV13) era in Taiwan. METHODOLOGY: From March 2014 to March 2015 a total of 500 healthy children and their households (631 adults) were enrolled from two large medical centres for nasopharyngeal carriage survey. Clinical isolates were prospectively collected from June 2012 to May 2015 at Chang Gung Memorial Hospital. We applied a multiplex polymerase chain reaction in addition to culture to detect S. pneumoniae. RESULTS: S. pneumoniae was isolated from 12.0 % of the children and 3.6 % of the households. In the children's cohort only 23.3 % of the isolates could be assigned to PCV13 serotypes; non-vaccine serotypes were predominant (76.6 %) and the most frequently detected non-vaccine serotypes were 15A/F and 15B/C (both 13.3 %), followed by 23A (6.7 %). In the household cohort, 21.7 % belonged to PCV13 serotypes, and 78.3 % to non-vaccine serotypes. Clinical analysis of culture-confirmed pneumococcal infection showed that infection caused by PCV13 serotypes decreased by 47 % from 83 % in 2012-2013 to 44 % in 2014-2015, while infection caused by non-PCV13 serotypes increased from 17 to 56 %. Among the carriage isolates a significantly higher percentage belonged to serogroup 15 compared to serogroup 19 (26.6 vs 6.66 %, 2014-2015; P=0.003). Therefore, clinical isolates belonging to serogroup 15 were more prevalent than those belonging to serogroup 19 (44.1 vs 32.3 %, 2014-2015; P=0.318). CONCLUSION: The isolation of non-vaccine serotypes and unknown serotypes after the introduction of PCV13 in children highlights the importance of continued surveillance for emerging serotypes.

Rise of community-onset urinary tract infection caused by extended-spectrum ß-lactamase-producing Escherichia coli in children.

BACKGROUND: Urinary tract infection (UTI) caused by resistant bacteria is becoming more prevalent. Few studies are available regarding community-onset UTIs caused by extended-spectrum ß-lactamase (ESBL)-producing bacteria in children. MATERIALS AND METHODS: During a 5-year period, hospitalized children with community-onset UTI caused by ESBL-producing Escherichia coli (case) and those with non-ESBL-producing E. coli (control) were identified. Patients with long-term care facility stay within the preceding month and those with urine cultures obtained >72 hours after admission were excluded. Clinical features and risk factors associated with the occurrence of ESBL-producing E. coli UTI were reviewed. RESULTS: The prevalence of UTI due to ESBL-producing E. coli increased slightly from 0.59% in 2002 to 0.96% in 2006. A total of 104 cases and 208 controls were included for comparison. The ciprofloxacin resistance of the ESBL-producing E. coli increased significantly in this period (p = 0.006). Pre-existing neurological diseases (p < 0.001), use of antibiotics in the past 3 months (p < 0.001), and recent hospitalization within 1 month (p < 0.001) were found to be potential risk factors. Moreover, previous exposure to third-generation cephalosporins (p < 0.001) and aminoglycosides (p < 0.001) was associated with the selection of ESBL-producing E. coli. Children with ESBL-producing E. coli UTIs had a longer hospital stay (p = 0.031) than those without. CONCLUSIONS: ESBL-producing E. coli gradually became coresistant to other broad-spectrum antibiotics, notably ciprofloxacin. UTIs caused by such resistant organisms led to a longer hospital stay and more antibiotic use. Reinforcement of infection control measures, especially hand washing in childcare settings and antibiotic stewardship, is critical to reduce the spread of ESBL-producing E. coli.