Aims: Polymyxins are an important last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Nonetheless, the emergence of polymyxin-resistance and the limiting of polymyxin monotherapy urgently demands its optimisation. Aquilaria malaccensis (Agarwood) has been widely used as traditional medicine. Many parts of the plant including leaves exhibit a considerable in vitro antibacterial activity against microbial pathogens. Exploiting A. malaccensis in combination with polymyxins provides a novel strategy in fighting antimicrobial resistance. The objective of this study was to evaluate the combination effects of A. malaccensis extract with polymyxins against Acinetobacter baumannii and Klebsiella pneumoniae. Methodology and results: In vitro time-kill studies and GC-MS analysis were performed to evaluate the bacterial killing of polymyxin B and extract combination and analyse chemical compounds of the extract, respectively. The combination of polymyxin B (1 mg/L) and A. malaccensis extract (32 mg/mL and 64 mg/mL) treatments exhibited enhanced bacterial killing compared to polymyxin B alone at 4 h and 24 h. Combination treatments also inhibited the bacterial growth of both A. baumannii and K. pneumoniae observed throughout the 24 h. More than sixty compounds including phytol, 9,12-octadecadienal, fatty acid, alkanes and terpenoids were putatively identified as the compounds that likely contributed to the antibacterial activity. Conclusion, significance and impact of study This study was the first to report the potential application of A. malaccensis extract in combination with polymyxin B in treatment against A. baumannii and K. pneumoniae and can be further investigated and optimized for the treatment of bacterial infectious diseases.
Thymelaeaceae ; Polymyxins ; Acinetobacter baumannii--immunology ; Klebsiella pneumoniae--immunology

Acinetobacter baumannii (A. Baumannii) is an emerging opportunistic pathogen responsible for hospital-acquired infections, and which now constitutes a sufficiently serious threat to public health to necessitate the development of an effective vaccine. In this study, a recombinant fused protein named OmpK/Omp22 and two individual proteins OmpK and Omp22 were obtained using recombinant expression and Ni-affinity purification. Groups of BALB/c mice were immunized with these proteins and challenged with a clinically isolated strain of A. baumannii. The bacterial load in the blood, pathological changes in the lung tissue and survival rates after challenge were evaluated. Mice immunized with OmpK/Omp22 fused protein provided significantly greater protection against A. baumannii challenge than those immunized with either of the two proteins individually. The results provide novel clues for future design of vaccines against A. baumannii.
Acinetobacter Infections ; pathology ; prevention & control ; Acinetobacter baumannii ; genetics ; immunology ; Animals ; Antibodies, Bacterial ; blood ; Bacterial Load ; Bacterial Outer Membrane Proteins ; genetics ; immunology ; Bacterial Vaccines ; immunology ; Disease Models, Animal ; Female ; Mice, Inbred BALB C ; Pneumonia, Bacterial ; pathology ; prevention & control ; Recombinant Fusion Proteins ; genetics ; immunology

OBJECTIVETo observe and investigate the risk factors and pathogen diversification of nosocomial lower respiratory infections in patients with hematological malignancy after chemotherapy.

METHODSRespiratory tract microbial population of fifty patients with different kinds of hematological malignancy and para-prepared to chemotherapy was quantitatively analyzed before and after chemotherapy at an arranged time from April, 2004 to December, 2005. Susceptibility test was determined for bacterium of nosocomial infection, and the homology of the same species of the bacteria was analyzed by a pulsed field gel electrophoresis (PFGE).

RESULTSIncidence rate of lower respiratory infections in patients with the hematological malignant after chemotherapy was 16%. The major nosocomial infectious pathogens were Acinetobacter spp; Escherichia coil and Fungus. Among them, Acinetobacter spp, were highly resistant to cephalosporins, quinolones, aminoglycosides, carbapenems and antibiotic with enzyme inhibitor, respectively but susceptible to Cefoperazone/Sulbactam belonging to antibiotic with enzyme inhibitor. And it was shown that there were two clones by the pulsed field gel electrophoresis (PFGE).

CONCLUSIONFollowing-up of nosocomial lower respiratory infection in patients with hematological malignancy after chemotherapy might offer theoretical evidence for the rational use of antibiotics and the control of nosocomial infections.

Acinetobacter baumannii ; drug effects ; isolation & purification ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Cross Infection ; epidemiology ; Escherichia ; drug effects ; isolation & purification ; Female ; Follow-Up Studies ; Hematologic Neoplasms ; drug therapy ; immunology ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Opportunistic Infections ; epidemiology ; Respiratory Tract Infections ; epidemiology