Introduction Pneumonia in children is a common disease yet determining its aetiology remains elusive. Objectives To determine the a) aetiology, b) factors associated with bacterial pneumonia and c) association between co-infections (bacteria + virus) and severity of disease, in children admitted with severe pneumonia. Methods A prospective cohort study involving children aged 1-month to 5-years admitted with very severe pneumonia, as per the WHO definition, over 2 years. Induced sputum and blood obtained within 24 hrs of admission were examined via PCR, immunofluorescence and culture to detect 17 bacteria/viruses. A designated radiologist read the chest radiographs. Results Three hundred patients with a mean (SD) age of 14 (±15) months old were recruited. Significant pathogens were detected in 62% of patients (n = 186). Viruses alone were detected in 23.7% (n = 71) with rhinovirus (31%), human metapneumovirus (HMP) [22.5%] and respiratory syncytial virus (RSV) [16.9%] being the commonest. Bacteria alone was detected in 25% (n = 75) with Haemophilus influenzae (29.3%), Staphylococcus aureus (24%) and Streptococcus pneumoniae (22.7%) being the commonest. Co-infections were seen in 13.3% (n = 40) of patients. Male gender (AdjOR 1.84 [95% CI 1.10, 3.05]) and presence of crepitations (AdjOR 2.27 [95% CI 1.12, 4.60]) were associated with bacterial infection. C

BackgroundCarbapenem resistant Enterobacteriaceae is a growing concern worldwide including Malaysia. The emergence of this pathogen is worrying because carbapenem is one of the 'last-line' antibiotics. The main objective of this study was to determine the prevalence of genetic mechanisms and clinical risk factors of carbapenem resistant Klebsiella pneumoniae (K. pneumoniae) in Malaysia.MethodsIn this study, seventeen carbapenem resistant K. pneumoniae strains isolated from a tertiary teaching hospital in 2013 were studied. Minimal inhibitory concentration (MIC) of the bacterial strains was determined and genes associated with carbapenemases and extended-spectrum-beta-lactamases (ESBLs) were sequenced and compared with the closest representatives published in public domains. All strains were also sub-typed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Statistical analyses were performed to determine the correlation between risk factors for acquiring carbapenem resistant K. pneumoniae and in-hospital mortality.ResultsThe predominant carbapenemase was bla OXA-48, detected in 12 strains (70.59%). Other carbapenemases detected in this study were bla KPC-2, bla IMP-8, bla NMC-A and bla NDM-1. Nine different pulsotypes were identified and nine strains which were affiliated with ST101, the predominant sequence type had similar PFGE patterns (similarity index of 85%). Based on univariate statistical analysis, resistance to imipenem and usage of mechanical ventilation showed a statistically significant effect separately to in-hospital mortality.ConclusionThe diverse genetic mechanisms harbored by these carbapenem resistant K. pneumoniae facilitates its spread and complicates its detection. Thus, correlation between microbiological trends with host characteristics and clinical factors will provide a better insight of rational treatment strategies and pathogen control.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.

The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring bla NDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1 H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1 H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.

Introduction Respiratory tract infections in children can result in respiratory sequelae. We aimed to determine the prevalence of, and factors associated with persistent respiratory sequelae 1 year after admission for a lower respiratory tract infection (LRTI). Methodology This prospective cohort study involved children 1 month to 5‐years‐old admitted with an LRTI. Children with asthma were excluded. Patients were reviewed at 1‐, 6‐, and 12‐months post‐hospital discharge. The parent cough‐specific quality of life, the depression, anxiety, and stress scale questionnaire and cough diary for 1 month, were administered. Outcomes reviewed were number of unscheduled healthcare visits, respiratory symptoms and final respiratory diagnosis at 6 and/or 12 month‐review by pediatric pulmonologists. Results Three hundred patients with a mean ± SD age of 14 ± 15 months old were recruited. After 1 month, 239 (79.7%) returned: 28.5% (n = 68/239) had sought medical advice and 18% (n = 43/239) had cough at clinic review. Children who received antibiotics in hospital had significantly lower total cough scores (P = .005) as per the cough diary. After 1 year, 26% (n = 78/300) had a respiratory problem, predominantly preschool wheezing phenotype (n = 64/78, 82.1%). Three children had bronchiectasis or bronchiolitis obliterans. The parent cough‐specific quality of life (PCQOL) was significantly lower in children with respiratory sequelae (P < .01). In logistic regression, the use of antibiotics in hospitals (adjusted odds ratio, 0.46; P = .005) was associated with reduced risk of respiratory sequelae. Conclusion In children admitted for LRTI, a quarter had respiratory sequelae, of which preschool wheeze was the commonest. The use of antibiotics was associated with a lower risk of respiratory sequelae.

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Streptococcus pneumoniae (S. pneumoniae) is one of the main causative agents of pneumococcal diseases. To date, more than 90 distinct serotypes have been identified. Implementation of vaccines has caused a drastic reduction in vaccine-serotype pneumococcal diseases but increase in cases due to non-vaccine serotype has been observed in Malaysia. However, further investigation on different serotype incidence in Malaysia is needed and the rate of pneumococcal vaccination for new-born babies in Malaysia remains low. The recent emergence of drug-resistant S. pneumoniae (DRSP) has also been a global concern, especially penicillin resistance. This study determined the serotypes of S. pneumoniae strains (n = 95) isolated from nasopharyngeal specimens from children admitted to UMMC from 2013 to 2015. In accordance with previous studies, PCR result showed 40% of NT isolates were successfully typed as 3 less common serotypes, namely 9N/L, 17A, and 23B. The repetitive-element PCR (REP-PCR) result revealed genetic variations among the strains whereby five major clusters were observed at the similarity of 80% by clustering analysis based on fingerprint data. Penicillin-binding proteins (pbps) of selected isolates were studied by PCR and sequencing. Three strains with ≤19-mm diameter zone for Oxacillin Disc Diffusion (ODD) test previously were recorded to have mutation on all pbp1a, pbp2b, and pbp2x with MIC of 4 µg/ml, which were penicillin-intermediate resistance according to the CLSI breakpoints.

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76–80%), ticarcillin-clavulanate (58–76%), and piperacillin-tazobactam (48–50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.