BACKGROUND AND PURPOSECigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD. EXPERIMENTAL APPROACHAndrographolide was given i.p. to BALB/c mice daily 2 h before 4% cigarette smoke exposure for 1 h over five consecutive days. Bronchoalveolar lavage fluid and lungs were collected for analyses of cytokines, oxidative damage markers and antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to cigarette smoke extract (CSE) and used to study the antioxidant mechanism of action of andrographolide. KEY RESULTSAndrographolide suppressed cigarette smoke-induced increases in lavage fluid cell counts; levels of IL-1b, MCP-1, IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3-nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to antioxidant response element (ARE) and total cellular glutathione level in response to CSE. Andrographolide up-regulated ARE-regulated gene targets including glutamate-cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR and heme oxygenase-1 in BEAS-2B cells in response to CSE. CONCLUSIONSAndrographolide possesses antioxidative properties against cigarette smoke-induced lung injury probably via augmentation of Nrf2 activity and may have therapeutic potential for treating COPD. BJP

A premature neonate had a catheter-associated bloodstream infection due to Staphylococcus lugdunensis. The MIC of oxacillin for the strain was >256 g/ml, and the mecA gene of S. lugdunensis was detected by PCR. The infection was resolved after removal of the line and treatment with vancomycin for 2 weeks. CASE REPORTA baby boy was delivered by caesarean section at 29 weeks of gestation with a birth weight of 980 g. Initial problems included grade III hyaline membrane disease, patent ductus arteriosus, and pulmonary hemorrhage. On day 8 of life, a long line was inserted into the left cubital fossa. On day 23, the baby developed sepsis. He had recurrent apnea and bradycardia requiring him to receive assisted ventilation. The level of Creactive protein was elevated, at 125.5 mg/liter. The total white cell count was 14 ϫ 10 9 /liter, and the immature neutrophil-tototal neutrophil ratio was 0.04. Thrombocytopenia (platelet count, 67 ϫ 10 9 /liter) was also present. Based on empirical evidence, the baby was started on cloxacillin and gentamicin. Two species of staphylococci were isolated from blood cultures taken before antibiotic administration. Both strains were resistant to cloxacillin. Treatment was changed to vancomycin after the baby had been on cloxacillin and gentamicin for 3 days. The long line was removed on the fifth day of infection, when one of the isolated organisms was confirmed to be Staphylococcus lugdunensis; the other isolate was reported to be a coagulasenegative staphylococcus. The culture of the long line tip also yielded S. lugdunensis. The chest X ray showed right upper lobe pneumonia. The results of a cranial ultrasound and a two-dimensional echocardiogram were normal. The baby showed good response to treatment with vancomycin. The level of C-reactive protein decreased to 7.3 mg/liter (on day 13 of vancomycin treatment), and the platelet count increased to 141 ϫ 10 9 /liter (on day 9 of vancomycin treatment). A repeat blood culture was still positive 48 h after vancomycin treatment was started but was negative by day 7. Vancomycin treatment was continued for a total of 2 weeks, with good clinical response. This is the first case report in the English-language literature of an infection due to an S. lugdunensis isolate carrying the mecA gene. Kawaguchi et al. detected mecA in one of two strains of S. lugdunensis in 1996 during a survey of staphylococcal isolates, but no description of clinical infection was given (5). As far as we are aware, this is also the first documentation of S. lugdunensis causing bloodstream infection in a neonate.As noted above, there were two isolates from the first blood culture. Both were characterized as staphylococci by Gram stain, colonial morphology, and a positive catalase reaction. The first isolate was a coagulase-negative staphylococcus with a typical negative reaction in both the latex agglutination test for clumping factor and protein A (BACTi Staph; Remel, Lenexa, Kans.) and the tube coagulase test with rabbit plasma. The second isolate had slightly yellow...

The need for hospitalisation was significantly associated with breathlessness and co-morbidity. There was minimal morbidity and no mortality observed. We attribute this to early presentation, diagnosis and treatment.

A 66-year-old man with four indwelling ventriculoperitoneal shunts for multiloculated hydrocephalus from a complicated case of meningitis a year before developed shunt infection based on a syndrome of fever, drowsiness, and cerebrospinal fluid neutrophil pleocytosis in the background of repeated surgical manipulation to relieve successive shunt blockages. The cerebrospinal fluid culture, which yielded a motile Enterococcus species, was believed to originate from the gut. This isolate was lost in storage and could not be characterized further. The patient improved with vancomycin and high-dose ampicillin therapy. He relapsed a month later with Enterococcus gallinarum shunt infection, which responded to high-dose ampicillin and gentamicin therapy. This is probably the first case report of motile Enterococcus infection of the central nervous system. CASE REPORTA 64-year-old man was admitted to a public hospital in early March 1999 for fever for 2 days. He had a background history of listeria meningitis a year ago, which was complicated by multiloculated hydrocephalus requiring four indwelling ventriculoperitoneal (VP) shunts. He also had mild Parkinson's disease for which he was not on any specific treatment and a recent admission, 2 months ago, to another hospital for aspiration pneumonia after which he was on a nasogastric tube for feeding. On examination, he was febrile (temperature, 38.0°C) and lethargic but oriented. His neck was supple, and the 4-VP shunts were palpable. A computed tomography (CT) scan of the brain showed no hydrocephalus, and the 4-VP shunts were in situ. He was empirically treated for presumed aspiration pneumonia with ceftriaxone and metronidazole, although the chest X-ray was unremarkable. As his fever persisted, therapy was changed to ceftazidime and vancomycin. The fever settled after about a week of treatment, and the antibiotics were stopped. Four days later, vancomycin was restarted because he became febrile and drowsy after a shunt revision from which cultures of the shunt and cerebrospinal fluid (CSF) were sterile. Subsequently, he required two further shunt revisions during the first week of April 1999. Cultures from the CSF fluid from these revisions yielded a motile Enterococcus species which correlated with significant neutrophil pleocytosis from the specimens of the CSF on both occasions. The organism was intermediate in its sensitivity to vancomycin (the vancomycin MIC was 8 mg/liter) and was sensitive to ampicillin, penicillin (the MIC of penicillin was 0.38 mg/liter), and gentamicin synergy. Shunt infection was diagnosed based on the preceding features and the ongoing fever and drowsiness in the patient. High-dose ampicillin was added to vancomycin, resulting in marked defervescence after 2 days. The treatment was continued for 3 weeks with good response. The shunts remained indwelling, as the surgeons were not keen to remove them. He underwent another shunt revision 2 weeks later, and this time the CSF culture was sterile. He was discharged after 6 weeks of hospitalization...

Acute suppurative thyroiditis (AST), a potential complication of pyriform sinus fistula (PSF), is a rare clinical condition as the thyroid gland is remarkably resistant to infections. Lack of awareness of the entity contributes to the rarity and frustrating recurrences. We performed a retrospective review of all cases of AST due to PSF treated at our institution over a 10-year period. The clinical data, investigations, operative findings and procedures, microbial culture reports and follow-up were recorded and analyzed. Between January 1997 and September 2006, 12 cases (8 males and 4 females) of AST due to PSF were treated. Nine patients (75%) underwent successful complete excision, seven of whom had initial incision and drainage procedures. In three patients (25%) with recurrence, one underwent complete excision at a later procedure, one patient had multiple recurrences with six incision and drainage procedures and two failed attempts of excision of PSF before final successful complete excision. The third patient is awaiting re-excision of the PSF tract. All patients, except the one awaiting re-excision, are well with no further recurrences during the follow-up period that ranged from 18 to 96 months (median, 46.5 months). AST due to PSF is a challenging entity in terms of diagnosis and management as recurrences are common despite meticulous dissection. High index of suspicion and radiological investigations such as barium studies and computed tomography scan aid in the delineation and excision of the fistulous tract.

Streptococcus pneumoniae remains a leading cause of serious paediatric disease. However, there are few published epidemiological data regarding invasive pneumococcal disease (IPD) in many countries in South East Asia, including Singapore. Baseline data for IPD are essential to inform policy regarding pneumococcal conjugate vaccine (PCV) use in Singapore. To our knowledge, this is the first study to use multilocus sequence typing (MLST) to investigate clonal relationships among Singaporean IPD isolates. We characterized 86 invasive pneumococci isolated from Singaporean children between 2001 and 2006 using serotyping and MLST. The objectives were to compare Singaporean MLST data to worldwide data and to assess serotype distribution in relation to current PCV formulations. We observed 50 sequence types (STs), a high proportion of which (n516) were novel STs. Despite the presence of these novel STs, serotype distribution was similar to that observed elsewhere. Serotypes 14, 6B, 19A and 19F accounted for 85 % of IPD cases. PCV7, PCV10 and PCV13 covered 85 %, 86 % and 97 % of IPD isolates, respectively. We have demonstrated a pressing need for larger studies to determine the molecular epidemiology and antibiotic susceptibility of circulating pneumococcal clones from both carriage and disease in Singapore. INTRODUCTIONDespite the fact that Streptococcus pneumoniae remains a leading cause of pneumonia and invasive disease in children worldwide, there are few published epidemiological data regarding invasive pneumococcal disease (IPD) in South East Asian countries. Existing data regarding the epidemiology of S. pneumoniae in Singapore have focussed on disease presentation (Low et al., 2007) or antibiotic resistance (Song et al., 2004a, b). Two previous studies have investigated serotype distribution among Singaporean childhood IPD isolates from 1997-1999 (n5180) and 1997-2004 (n5147) (Chong et al., 2008;Soh et al., 2000).Baseline data regarding the serotype prevalence of IPD are essential to inform policy around the use of pneumococcal conjugate vaccines (PCVs) in Singapore. PCV7 has been available on a demand basis in Singapore since October 2005 but was only incorporated into the national childhood vaccination schedule in November 2009 (Vasoo et al., 2010).Information that aids in understanding the genetic background of pneumococci associated with IPD is also important; the invasive potential of individual clones to succeed and spread geographically is associated with genotype as well as serotype (Hanage et al., 2005; Henriques-Normark et al., 2008;Sandgren et al., 2004). Clonal expansion has been shown to result in notable changes in circulating pneumococcal populations even in the absence of vaccine pressure.To our knowledge, no published study has used multilocus sequence typing (MLST) to characterize Singaporean pneumococcal disease isolates. The objective of this study was to characterize pneumococci isolated from IPD in Singaporean children using serotyping and MLST and compare these data to data from elsewh...

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Background The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD. Methods A retrospective study of infants ≤ 90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared. Results A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD. Conclusions The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.