Using beta-lactamase to trigger supramolecular hydrogelation.
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Catalysis↗
Biomedical subjects
Pak-Leung Ho
Publications and source records attributed to Pak-Leung Ho.
Molecular epidemiology and household transmission of community-associated methicillin-resistant Staphylococcus aureus in Hong Kong.
This study evaluated the clinical and epidemiologic features of individuals with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Hong Kong from January 2004 through December 2005. Twenty-four episodes of skin and soft tissue infections and 1 episode of meningitis due to CA-MRSA were identified. CA-MRSA infections or carriage was found in 6 (13%) of 46 household contacts. A total of 29 isolates were analyzed by the Staphylococcus cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. In addition, polymerase chain reaction detection of the genes encoding Panton-Valentine leukocidin was also carried out. It was observed that 24 had SCCmec IV/IVA and 5 had SCCmec V, and 23 were pvl positive. PFGE analysis clustered all except 1 isolate into 3 pulsed-field types (PFTs), HKU100 through HKU300. The HKU100 isolates had genotype ST30-IV identical to the Southwest Pacific clone. The HKU200 isolates belonged to ST59-V and were multiresistant, including an ermB-mediated macrolide resistance trait, which is characteristic of the predominant CA-MRSA clone in Taiwan. The HKU300 isolates had unique features (ST8, Panton-Valentine leukocidin negative, and SCCmec IVA) typical of CA-MRSA in Japan. In conclusion, CA-MRSA has a propensity to spread within families. Our findings showed that CA-MRSA strains in Hong Kong have diverse genetic backgrounds.
Adolescent↗
Diagnostic application of genotypic identification of mycobacteria.
This study evaluated conventional methods, GLC and three molecular tests, including 16S rRNA sequencing, for the identification of mycobacteria, and the experiences of the authors with the integration of these methods into a diagnostic clinical laboratory were also recorded. Of 1067 clinical isolates of mycobacteria identified by conventional tests, 365 were tested by Accuprobe hybridization assays and PCRs specific for Mycobacterium tuberculosis (MTB) complex or Mycobacterium avium complex (MAC), 202 were tested by 16S rRNA sequencing, and 142 were tested by GLC. Three runs of all tests were performed on a weekly basis. The identifications for 209 MTB complex and 118 MAC isolates obtained by species-specific PCR were in complete agreement with AccuProbe hybridization and conventional test results. The 16S rRNA sequence-based identification, at a similarity of > or =99 %, for 132 of 142 isolates was concordant with the identifications made by the biochemical methods, and for 134 isolates was concordant with the identifications made by GLC at species, group or complex level. 16S rRNA sequencing resulted in fewer incorrectly identified or unidentified organisms than GLC or conventional tests. For the slowly growing non-tuberculous mycobacteria, the mean turnaround times for identification were 4-5 days for 16S rRNA sequencing, 14-29 days for GLC and 22-23 days for conventional methods. Considering the large proportion of some species among clinical isolates, a strategy of initial screening with species-specific PCR (or AccuProbe assays) for the MTB complex and MAC, followed by direct sequencing of the strains that yield negative results, should make 16S rRNA sequencing more affordable for routine application in diagnostic laboratories.
Algorithms↗
Fulminant community-acquired Acinetobacter baumannii pneumonia as a distinct clinical syndrome.
STUDY OBJECTIVES: Acinetobacter baumannii (AB) is an important cause of hospital-acquired pneumonia (HAP), and an uncommon but important cause of community-acquired pneumonia (CAP) with high mortality. To better characterize CAP-AB, we compared its clinical features and outcomes with a control group of HAP-AB patients. METHODS: This is a retrospective case-control study comparing CAP-AB and HAP-AB patients, which was performed at United Christian Hospital between July 2000 and December 2003. RESULTS: There were 19 cases of CAP-AB and 74 cases of HAP-AB. When compared with the HAP-AB group, the CAP-AB group had more ever-smokers (84.3% vs 55.4%, respectively; p = 0.031), more COPD patients (63.2% vs 29.7%, respectively; p = 0.014), and fewer median days of hospitalization (HAP-AB group, median, 0 days; CAP-AB group, 0 days [range, 0 to 30 days]; p = 0.049) in the previous year. The CAP-AB group had more patients with positive blood culture findings (31.6% vs 0%, respectively; p < 0.001), a higher frequency of ARDS (84.2% vs 17.6%, respectively; p < 0.001), and disseminated intravascular coagulation (DIC) (57.9% vs 8.1%, respectively; p < 0.001). The median survival time was only 8 days in the CAP-AB group, vs 103 days in the HAP-AB group (p = 0.003). Factors associated with the higher mortality in the CAP-AB group included the presence of AB bacteremia (p = 0.040), platelet count of < 120 x 10(9) cells/L (p = 0.026), pH < 7.35 on presentation (p = 0.047), and the presence of DIC (p = 0.004). CONCLUSIONS: CAP-AB appears to be a unique clinical entity with a high incidence of bacteremia, ARDS, DIC, and death, when compared to HAP-AB. Further studies are needed to investigate the mechanism of the fulminant nature of CAP-AB.
Acinetobacter Infections↗
Cloning and characterization of a chromosomal class C beta-lactamase and its regulatory gene in Laribacter hongkongensis.
Laribacter hongkongensis, a newly discovered bacterium recently shown to be associated with community-acquired gastroenteritis, is generally resistant to most beta-lactams except the carbapenems. We describe the cloning and characterization of a novel chromosomal class C beta-lactamase and its regulatory gene in L. hongkongensis. Two genes, ampC and ampR, were cloned by inserting restriction fragments of genomic DNA from L. hongkongensis strain HLHK5 into pBK-CMV to give the recombinant plasmid pBK-LHK-5. The ampR and ampC genes and their promoters were divergently oriented, with the ampR gene immediately upstream of the ampC gene and an intercistronic Lys-R motif, typical of inducible ampC-ampR regulatory systems. The deduced amino acid sequence of the cloned AmpC beta-lactamase (pI 8.1) contained consensus motifs characteristic of class C beta-lactamases but had identities no greater than 46% to known class C beta-lactamases. The kinetic properties of this AmpC were also compatible with those of a class C beta-lactamase. PCR of 20 clinical isolates of L. hongkongensis, including HLHK5, showed the presence of both ampC and ampR genes in all isolates. Southern hybridization suggested that the ampC gene of HLHK5 was chromosomally encoded. Subcloning experiments showed that the expression of the ampC gene of HLHK5 was regulated by its ampR gene, which acts as a repressor. The beta-lactamase characterized from strain HLHK5 was named LHK-5 (gene, bla(LHK-5)) and represents the first example of AmpC beta-lactamase in the beta subdivision of proteobacteria.
Amino Acid Sequence↗
Recurrent bacteraemia caused by different Salmonella species in a systemic lupus erythematosus patient.
Non-typhoidal Salmonella infections are increasingly being encountered. Recurrent systemic salmonellosis has previously been reported in both immunocompromised and immunocompetent hosts. However, recurrent salmonella bacteraemia by different species of salmonella has rarely been described. We report a patient with systemic lupus erythematosus having Salmonella enteritidis and Salmonella typhimurium infections after ingesting raw eggs and vegetables. Multiple internal organs, including left knee joint, left ovary and bones, were involved. The patient recovered with a prolonged course of antibiotics. This case illustrates that recurrent systemic salmonellosis can be caused by different species of pathogens, especially in immunocompromised hosts. Detailed food history and education on food hygiene is essential in making the diagnosis and preventing recurrence. A prolonged course of antibiotics may be needed to manage these cases.
Adult↗
Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome.
BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) occurred in our 22-bed intensive care unit (ICU; Prince of Wales Hospital, Hong Kong, HKSAR, China) from 12 March to 31 May 2003, when only patients with SARS were admitted. This period was characterized by the upgrading of infection control precautions, which included the wearing of gloves and gowns all the time, an extensive use of steroids, and a change in antibiotic prescribing practices. The pattern of endemic pathogenic organisms, the rates of acquisition of methicillin-resistant Staphylococcus aureus (MRSA), and the rates of ventilator-associated pneumonia (VAP) were compared with those of the pre-SARS and post-SARS periods. METHODS: Data on pathogenic isolates were obtained from the microbiology department (Prince of Wales Hospital). Data on MRSA acquisition and VAP rates were collected prospectively. MRSA screening was performed for all ICU patients. A case of MRSA carriage was defined as an instance in which MRSA was recovered from any site in a patient, and cases were classified as imported or ICU-acquired if the first MRSA isolate was recovered within 72 h of ICU admission or after 72 h in the ICU, respectively. RESULTS: During the SARS period in the ICU, there was an increase in the rate of isolation of MRSA and Stenotrophomonas and Candida species but a disappearance of Pseudomonas and Klebsiella species. The MRSA acquisition rate was also increased: it was 3.53% (3.53 cases per 100 admissions) during the pre-SARS period, 25.30% during the SARS period, and 2.21% during the post-SARS period (P<.001). The VAP rate was high, at 36.5 episodes per 1000 ventilator-days, and 47% of episodes were caused by MRSA. CONCLUSIONS: A SARS outbreak in the ICU led to changes in the pathogen pattern and the MRSA acquisition rate. The data suggest that MRSA cross-transmission may be increased if gloves and gowns are worn all the time.
Anti-Bacterial Agents↗
Excess hospital admissions for pneumonia, chronic obstructive pulmonary disease, and heart failure during influenza seasons in Hong Kong.
It is widely held that Southern China is a hypothetical influenza epicentre for the emergence of pandemic influenza viruses. However, influenza is perceived as a relatively unimportant infection in this part of the world compared with western countries. Hong Kong is situated within the hypothetical epicentre and serves as a sentinel post for the region. In a retrospective study, the influenza-associated excess hospitalisations in a regional hospital for pneumonia, chronic obstructive pulmonary disease (COPD), heart failure, and asthma in persons aged > or = 65 years from 1998 to 2001 were each estimated by a model taking into consideration the confounding effect of other respiratory viral infections, seasonal factors, time trends, and weather and pollution indices. In the regression models, influenza activity is an independent significant factor affecting admission rates for pneumonia, COPD, and heart failure but not that for asthma. The variations in hospital admissions for pneumonia, COPD, and heart failure explained by influenza activity were 38.9, 7.5, and 45.6%, respectively. The adjusted rates of excess influenza-associated hospital admissions for the three diagnoses combined amounted to 58.5, 20.0, 29.2, and 13.4 per 10,000 populations aged > or = 65 years in 1998, 1999, 2000, and 2001, respectively. In conclusion, influenza activity is associated significant excess hospital admissions among elderly aged 65 or above in Hong Kong, comparable to the data reported in Western countries. The findings support a wider application of annual influenza vaccination in this region.
Aged↗
Fluoroquinolone and other antimicrobial resistance in invasive pneumococci, Hong Kong, 1995-2001.
We determined the susceptibilities of 265 invasive isolates of pneumococci obtained during 1995 to 2001 in Hong Kong to 11 antimicrobial agents and their serotypes. Overall, 62.6% isolates were susceptible to penicillin, 20% were intermediately resistant, and 17.4% were resistant. The overall prevalence of levofloxacin resistance (MIC > or = 8 microg/mL) was 3.8% but increased to 15.2% among the penicillin-resistant isolates. All levofloxacin-resistant isolates were clonally related; had reduced susceptibility to penicillin, cefotaxime, and clarithromycin; and were derived from adults > or = 50 years of age. Of the penicillin-nonsusceptible pneumococci, 90% from children < or = 5 years of age and 54.8% from persons of all ages were of serotypes that are included in the 7-valent pneumococcal conjugate vaccine; 93.5% from children < or = 5 years of age and 93% from persons of all ages were of serotypes that are included in the 23-valent polysaccharide vaccine.
Adolescent↗
Decreased levofloxacin susceptibility in Haemophilus influenzae in children, Hong Kong.
Among 563 strains of Haemophilus influenzae from young children in Hong Kong, 5 (0.9%) had decreased susceptibility to quinolones. The five strains had a Ser-84-Lys or Asp-88-Asn substitution in GyrA. Pulsed-field gel electrophoresis showed that the isolates are genetically diverse.
Anti-Bacterial Agents↗
Using biofunctional magnetic nanoparticles to capture vancomycin-resistant enterococci and other gram-positive bacteria at ultralow concentration.
Covalently linked to vancomycin (Van), chemically stable and highly magnetic anisotropic FePt magnetic nanoparticles (3-4 nm) become water-soluble and capture vancomycin-resistant enterococci (VRE) and other Gram-positive bacteria at concentrations approximately 10(1) cfu/mL via polyvalent ligand-receptor interactions. When a pyramidal end of a magnet "focuses" the nanoparticles into approximately 1 mm(2) area, the bacteria can be observed by an optical microscope and further identified by electron micrograph (EM). Compared to the conventional use of magnetic particles (with the sizes of 1-5 microm) in biological separation or drug delivery, magnetic nanoparticles, combined with specific receptor-ligand interactions, promise a sensitive and rapid protocol to detect pathogens.
Alloys↗
Multivalent antibiotics via metal complexes: potent divalent vancomycins against vancomycin-resistant enterococci.
Dimers of vancomycin (Van), linked by a rigid metal complex, [Pt(en)(H(2)O)(2)](2+), exhibit potent activities (MIC approximately 0.8 mug/mL, approximately 720 times more potent than that of Van itself) against vancomycin-resistant enterococci (VRE). The result suggests that combining metal complexation and receptor/ligand interaction offers a useful method to construct multivalent inhibitors.
Anti-Bacterial Agents↗
Using biofunctional magnetic nanoparticles to capture gram-negative bacteria at an ultra-low concentration.
After conjugation to vancomycin (Van), chemically stable and highly magnetic anisotropic FePt magnetic nanoparticles (approximately 4 nm) become water-soluble and capture E. coli at 15 cfu mL(-1).
Journal Article↗
SARS: hospital infection control and admission strategies.
Nosocomial clustering with transmission to health care workers, patients and visitors is a prominent feature of severe acute respiratory syndrome (SARS). Hospital outbreaks of SARS typically occurred within the first week after admission of the very first SARS cases when the disease was not recognized and before isolation measures were implemented. In the majority of nosocomial infections, there was a history of close contact with a SARS patient, and transmission occurred via large droplets, direct contact with infectious material or by contact with fomites contaminated by infectious material. In a few instances, potential airborne transmission was reported in association with endotracheal intubation, nebulised medications and non-invasive positive pressure ventilation of SARS patients. In all SARS-affected countries, nosocomial transmission of the disease was effectively halted by enforcement of routine standard, contact and droplet precautions in all clinical areas and additional airborne precautions in the high-risk areas. In Hong Kong, where there are few private rooms for patient isolation, some hospitals have obtained good outcome by having designated SARS teams and separate wards for patient triage, confirmed SARS cases and step-down of patients in whom SARS had been ruled out. In conclusion, SARS represents one of the new challenges for those who are involved in hospital infection control. As SARS might re-emerge, all hospitals should take advantage of the current SARS-free interval to review their infection control programmes, alert mechanisms, response capability and to repair any identified inadequacies.
Algorithms↗
Carriage of methicillin-resistant Staphylococcus aureus, ceftazidime-resistant Gram-negative bacilli, and vancomycin-resistant enterococci before and after intensive care unit admission.
OBJECTIVE: To measure patients' risk for acquiring antibiotic-resistant microorganisms associated with intensive care unit admission. DESIGN: Prospective, observational study. SETTING: Ten public hospitals including one university medical center. PATIENTS: Consecutive patients admitted to ten intensive care units. INTERVENTIONS: Serial patient surveillance cultures were screened for vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus (MRSA), ceftazidime-resistant Gram-negative bacilli (CR-GNB), Acute Physiology and Chronic Health Evaluation II score, and antibiotic and medical device exposures. MEASUREMENTS AND MAIN RESULTS: A total of 1,697 patient admissions in ten intensive care units were enrolled. The overall carriage rate of antibiotic-resistant bacteria at intensive care unit entry was 12.1% for MRSA, 14% for CR-GNB and 4.7% for both. At discharge from the intensive care unit, new carriage of MRSA, CR-GNB, and both was found in 11.1%, 14.2%, and 2.4% of the patients, respectively. The acquisition rates in the individual units correlated highly and positively with proportion of patients with carriage at intensive care unit entry for both MRSA (n = 10, Pearson's r =.89, p < 0.001) and CR-GNB (n = 10, Pearson's r =.92, p < 0.001). By logistic regression, severity of illness (odds ratio, 1.4), length of stay (odds ratio, 1.7), use of penicillins (odds ratio, 1.9), and number of antibiotics (odds ratio, 1.2) and medical devices (odds ratio, 1.2) were independently associated with intensive care unit acquisition of MRSA. In comparison, variables independently associated with intensive care unit acquisition of CR-GNB were Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.5), number of antibiotics (odds ratio, 1.1), and artificial airway (odds ratio, 1.5). CONCLUSIONS: These data suggest that hospitalization in the intensive care unit introduces significant risk to patients in terms of transmission of MRSA and/or CR-GNB. This risk seems to be influenced strongly by the proportion of patients with colonization at intensive care unit admission and is associated with severity of illness, length of stay, and exposures to antibiotics and medical devices.
Aged↗
Detection of katG Ser315Thr substitution in respiratory specimens from patients with isoniazid-resistant Mycobacterium tuberculosis using PCR-RFLP.
Mutations in the katG locus of catalase peroxidase in Mycobacterium tuberculosis (MTB) account for major isoniazid (INH) resistance. In the South China region, a collection of 906 respiratory specimens and 142 MTB isolates was used to evaluate the sensitivity and specificity of a PCR-RFLP method for the detection of INH resistance-associated mutations. Except for four catalase-negative MTB isolates, katG PCR for a 620-bp amplicon was successful for all purified MTB isolates. For respiratory specimens, diagnostic sensitivity and specificity of katG PCR was 85 and 100 %. Subsequent RFLP of the katG amplicons by MspI digestion identified that 51 % of INH-resistant MTB were associated with the Thr315 phenotype, and that codon 463 was a polymorphic site with no linkage to INH resistance. The Arg463 wild-type MTB isolates predominant in the Western world were replaced by isolates carrying Leu463 in the South China region. RFLP patterns of katG amplicons from respiratory specimens were identical to those of the corresponding MTB cultured colonies. This method has potential application for rapid diagnosis of INH resistance due to katG Ser315Thr mutation.
Bacterial Proteins↗
Hydrophobic interaction and hydrogen bonding cooperatively confer a vancomycin hydrogel: a potential candidate for biomaterials.
Antibiotic hydrogels based on a vancomycin (Van) derivative, formed by self-assembling Van-pyrene (1) in water, using the pi-pi interaction of pyrene moieties and hydrogen bonding of Vans, promise a new way to make novel biomaterials.
Anti-Bacterial Agents↗
Bacteremia caused by Escherichia coli producing extended-spectrum beta-lactamase: a case-control study of risk factors and outcomes.
A case-control study was conducted in order to identify the risk factors associated with bloodstream infection caused by Escherichia coli producing extended-spectrum beta-lactamase (ESBL) and to determine the outcomes of infected patients. Risk factors associated with ESBL production, according to univariate analysis, included a history of recent hospitalization [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.1-8.9; p < 0.001], severe underlying diseases (OR 15, 95% CI 4.4-51.5; p < 0.001), prior exposure to urinary catheters (OR 8.3, 95% CI 3.2-21.7; p < 0.001) and nosocomial (OR 14.1, 95% CI 6.1-32.8; p < 0.001) or urinary (OR 3.6, 95% CI 1.7-7.4; p < 0.001) origin of the bacteria. Multivariate analysis revealed that severe underlying diseases (OR 31.2, 95% CI 6.7-144; p < 0.001) and nosocomial (OR 16.5, 95% CI 5.6-49; p < 0.001) and urinary origins (OR 7.8, 95% CI 2.6-23.8; p < 0.001) of the bacteria were independently associated with ESBL production in bacteremic E. coli. Crude mortality in case patients was more than twice as high as that in controls (p = 0.04). Production of ESBL increased the risk of inappropriate initial therapy (OR 95.6, 95% CI 27.4-334.2; p < 0.001). Treatment failed in 4/7 case patients treated with ceftazidime to which the isolate was susceptible in vitro. Our findings have implications for the choice of empirical therapy in nosocomial urinary tract infection.
Age Distribution↗