Increased nasopharyngeal carriage of serotypes 6A, 6C, and 6D Streptococcus pneumoniae after introduction of childhood pneumococcal vaccination in Hong Kong.

Active surveillance on nasopharygeal carriage of Streptococcus pneumoniae in children was conducted in 5581 children under 16 years old admitted with respiratory illness to the pediatric wards in a Hong Kong teaching hospital during 2008-2010. The isolation rate of S. pneumoniae was 14.5%. The most common serotypes/groups from 911 isolates were 19F, 6B, 23F, 14, 6C, 6A, and 3. Considering only children under 2 years old, the percentage serotype belonging to that of the 7-, 10- and 13-valent conjugate pneumococcal vaccines in S. pneumoniae were 56.0% (115/205), 57% (117/205), and 80.5% (165/205), respectively. The prevalence of penicillin-nonsusceptibility (MIC ≥4.0 µg/mL) was 9.1% and for cefotaxime (MIC ≥2.0 µg/mL) was 14.7%. A high prevalence of non-6B serotype, including 6A, 6C, and 6D was noted after the introduction of PCV7 conjugate pneumococcal vaccines in Hong Kong.

Role of 'atypical pathogens' among adult hospitalized patients with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Agents such as Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila are recognized as important causes of community-acquired pneumonia (CAP) worldwide. This study examined the role of these 'atypical pathogens' (AP) among adult hospitalized patients with CAP. METHODS: A prospective, observational study of consecutive adult CAP (clinico-radiological diagnosis) patients hospitalized during 2004-2005 was conducted. Causal organisms were determined using cultures, antigen testing and paired serology. Clinical/laboratory/radiological variables and outcomes were compared between different aetiologies, and a clinical prediction rule for AP was constructed. RESULTS: There were 1193 patients studied (mean age 70.8 +/- 18.0 years, men 59.3%). Causal organisms were identified in 468 (39.2%) patients: 'bacterial' (48.7%), 'viral' (26.9%), 'AP' (28.6%). The AP infections comprised Mycoplasma or Chlamydophila pneumoniae (97.8%) and co-infection with bacteria/virus (30.6%). The majority of AP infections involved elderly patients (63.4%) with comorbidities (41.8%), and more than one-third of patients were classified as 'intermediate' or 'high' risk CAP on presentation (pneumonia severity index IV-V (35.1%); CURB-65 2-5 (42.5%)). Patients with AP infections had disease severities and outcomes similar to patients with CAP due to other organisms (oxygen therapy 29.1% vs 29.8%; non-invasive ventilation 3.7% vs 3.3%; admission to the intensive care unit 4.5% vs 2.7%; length of hospitalization 6 day vs 7 day; 30-day mortality: 2.2% vs 6.0%; overall P > 0.05). Age <65 years, female gender, fever > or =38.0 degrees C, respiratory rate <25/min, pulse rate <100/min, serum sodium >130 mmol/L, leucocyte count <11 x 10(9)/L and Hb < 11 g/dL were features associated with AP infection, but the derived prediction rule failed to reliably discriminate CAP caused by AP from bacterial CAP (area under the curve 0.75). CONCLUSIONS: M. pneumoniae and C. pneumoniae as single/co-pathogens are important causes of severe pneumonia among older adults. No reliable clinical indicators exist, so empirical antibiotic coverage for hospitalized CAP patients may need to be considered.

Value of serum procalcitonin, neopterin, and C-reactive protein in differentiating bacterial from viral etiologies in patients presenting with lower respiratory tract infections.

The values of procalcitonin (PCT), neopterin, and C-reactive protein (CRP) alone and in combination to differentiate bacterial from viral etiology in patients with lower respiratory tract infections (LRTIs) were evaluated. Sera obtained on the day of hospitalization for LRTI from 139 patients with confirmed bacterial etiology and 128 patients with viral etiology were examined. A further 146 sera from healthy Chinese subjects with no infection were included as controls. The area under the receiver operating characteristic (ROC) curve (area under curve [AUC]) for distinguishing bacterial from viral infections was 0.838 for CRP and 0.770 for PCT (P < 0.05). The AUC for distinguishing viral from bacterial infections was 0.832 for neopterin (P < 0.05). When the markers were used in combination, AUC of ROC (CRP/neopterin) was 0.857, whereas (CRP x PCT)/neopterin was 0.856. Combination of 2 or all 3 of the biomarkers may improve the discriminatory power in delineating bacterial versus viral etiology in LRTI.

Viral etiology of acute exacerbations of COPD in Hong Kong.

INTRODUCTION: Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD). However, little is known about viral etiology related to AECOPD in Asia. We aimed to study the viral etiology of AECOPD in Hong Kong. METHODS: Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture. Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge. RESULTS: There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 +/- 7.7 years [+/- SD]; 160 men). Mean FEV(1) was 39.6 +/- 18.9% of predicted normal, and FEV(1)/FVC ratio was 58.0 +/- 15.2%. Fifty-eight episodes (22.1%) yielded positive viral PCR results. The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%). The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture. The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV(1) >or= 50%, >or= 30 to 50%, and < 30% of predicted normal. Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year CONCLUSION: Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong. These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD.

Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.

Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.

Longitudinally tracking fluoroquinolone resistance and its determinants in penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae isolates in Hong Kong, 2000 to 2005.

Of 1,388 Streptococcus pneumoniae isolates collected from 2000 to 2005, 10.5% had a ciprofloxacin MIC of >/=4.0 mug/ml and 1.6% (range, 0.8% to 4.3% per year) had a levofloxacin MIC of >/=4.0 mug/ml. Molecular characterization indicated that fluoroquinolone resistance occurred independently in our prevalent Spain(23F)-1 clone, expressing serotypes 23F, 19F, and 14. Rates of resistance to levofloxacin in S. pneumoniae have remained stable at a Hong Kong hospital.

Streptococcus suis in Hong Kong.

Streptococcus suis was isolated from 6.1% of raw pork meat from 3 of the 6 wet markets in 6 districts in Hong Kong. S. suis was particularly isolated in sites from the tongue, tonsil, bone, and tail, but not from lean meat/minced pork or internal organs. Isolates were confirmed by polymerase chain reaction using S. suis-specific primers, did not belong to serotype 2 using serotype 2-specific antiserum, and were clustered closely with other known serotypes by phylogenetic analysis. Ten strains from patients admitted to Hong Kong hospitals with sepsis or meningitis in the past 10 years all belonged to type 2, with closely related pulsed-field gel electrophoresis types that were distinct from the S. suis strains isolated from pork in this study. These methods may serve as useful tools in studying and enhancing our understanding of these infections in Hong Kong.

Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. AIM: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. METHODS: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. RESULTS: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). CONCLUSION: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.

Use of the housekeeping genes, gdh (zwf) and gki, in multilocus sequence typing to differentiate Streptococcus pneumoniae from Streptococcus mitis and Streptococcus oralis.

Polymerase chain reaction and sequencing of the housekeeping genes, gdh (zwf) and gki, based on the primers and alleles from multilocus sequence typing can be used to delineate and support the identity of clinical isolates of Streptococcus pneumoniae and differentiate from the closely related Streptococcus mitis and Streptococcus oralis.

Rapid screening of fluoroquinolone resistance determinants in Streptococcus pneumoniae by PCR-restriction fragment length polymorphism and single-strand conformational polymorphism.

A rapid method, using PCR-restriction fragment length and single-strand conformation polymorphism (SSCP), was applied to screen for mutations of the fluoroquinolone resistance determinants in Streptococcus pneumoniae. One hundred nonduplicate Streptococcus pneumoniae isolates with ciprofloxacin MICs of > or = 4.0 microg/ml from the Prince of Wales Hospital, Hong Kong, years 2000 to 2003, were examined. For each isolate, PCR amplicons of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE genes were digested with AluI, HinfI, Sau3AI, and MspI, respectively, and analyzed by SSCP. Each SSCP pattern was given a number, and each isolate obtained a four-digit code, e.g., 1111, that represented the SSCP profile. The SSCP patterns were correlated to mutations characterized from sequence analyses of PCR amplicons. The most common SSCP profile obtained was no. 5232 (40%), which included strains with two amino acid substitutions in the ParC (Lys-137-Asn) and ParE (Ile-460-Val) genes, followed by the SSCP profile 5223 (17%), which included strains with amino acid substitutions in the ParE (Ile-460-Val) gene only. Ten isolates (10%) with amino acid substitutions at GyrA and ParE (+/-ParC) genes were resistant to levofloxacin with a MIC of > or = 16 microg/ml. Other SSCP profiles were unique in distinguishing the common amino acid substitutions in GyrA (Ser-81-Phe) and ParC (Lys-137-Asn, Ser-79-Phe plus Lys-137-Asn, Asp-83-Asn plus Lys-137-Asn, Ser-79-Phe, and Glu-96-Asp). SSCP analysis of restricted fragments generated patterns that were highly discriminative for mutations present in the QRDRs of gyrA, gyrB, parC, and parE. This method provides a database of high resolution profiles on these mutations and allows rapid screening for new mutations of the fluoroquinolone resistance genes.