ABSTRACT
Search for anti-beta-lactamase and synthesis of newer penicillin were suggested to overcome resistance to penicillin in chemotherapy. It was found that clavulanic acid, an ant-beta-lactamase was ineffective due to its structural modification by bacteria. Thus, there is a need for the synthesis of newer pencillins. Retro-synthesis was inspired by the success of forward reaction i.e.conversion of penicillin G to 6-aminopenicillanic acid (6-APA) by biological process. In the present study a better enzymatic method of synthesis of newer pencillin by a beta-lactamase-free penicillin amidase produced by Alcaligenes sp. is attempted. Antibacterial and toxicological evaluation of the enzymatically synthesized beta-lactams are reported. Condensation of 6-APA with acyl donor was found to be effective when the reaction is run in dimethyl formamide (DMF 50% v/v) in acetate buffer (25 mM pH 5.0) at 37 degrees C. Periplasm entrapped in calcium alginate exihibited the highest yield (approximately 34%) in synthesis. The minimum inhibitory concentration of the synthetic products against Staphylococcus aureus and Salmonella typhi varied between 20-80 microg/ml. Some of the products exhibited antibacterial activity against enteric pathogens. It was interesting to note that product A was potent like penicillin G. LD50 value of three products (product A, B and C) was more than 12 mg/kg. Furthermore, these synthetic beta-lactams did not exihibit any adverse effect on house keeping enzymes viz., serum glutamate oxalacetate-trans-aminase, serum glutamate pyruvate -trans-aminase, acid phosphatase, alkaline phosphatase of the test animals. The hematological profile (RBC and WBC) of the test animals also remained unaffected.
Subject(s)
Alcaligenes/drug effects , Animals , Anti-Bacterial Agents/biosynthesis , Cells, Immobilized/enzymology , Lethal Dose 50 , Microbial Sensitivity Tests , Penicillin Amidase/metabolism , Staphylococcus aureus/drug effects , beta-Lactams/metabolismABSTRACT
La bacteriemia causada por Achromobacter xylosoxidans es rara y hay poca información con repecto a su tratamiento. La mayoría de los pacientes que han desarrollado bacteriemia por Achromobacter han presentado causas predisponentes a la infección. Se informa aquí un caso de bacteriemia y neumonía adquirida en la comunidad en un paciente previamente sano. Achromobacter es usualmente resistente a amplicilina, cefalosporinas de primera, segunda y tercera generación, aminoglucósidos y quinolomas. Piperacilina sola o en combinación con tazobactama, impenem y trimetoprima-sulfametozaxol inhiben la mayoría de los aislamientos.
Subject(s)
Humans , Male , Aged , Alcaligenes/isolation & purification , Bacteremia/microbiology , Community-Acquired Infections/microbiology , Pneumonia, Bacterial/microbiology , Aged, 80 and over , Alcaligenes/drug effects , Bacteremia/diagnosis , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapyABSTRACT
Objetivo: Avaliar desinfetantes de uso domiciliar, identificando a presença de bactérias contaminantes, e conhecer o nível de tolerância dessas bactérias ao cloreto de benzalcônio. Métodos: Foram adquiridos aleatoriamente no comércio da regiäo metropolitana de Säo Paulo, SP, Brasil, 52 amostras de desinfetantes de uso domiciliar para análise quanto à presença de bactérias contaminantes. O nível de tolerância dessas bactérias ao cloreto de benzalcônio foi determinado pelo método da macrodiluiçäo em caldo. Resultados: De 52 amostras, 16 (30,77 por cento) estavam contaminadas por bactérias Gram negativas, com contagens variando entre 104 e 106 UFC/ml. Esses contaminantes foram identificados como Alcaligenes xylosoxidans, Burkholderia cepacia e Serratia marcescens. As Concentraçöes Inibitórias Mínimas (CIM: mg/ml) do cloreto de benzalcônio para S. marcescens, A. xylosoxidans e B. cepacia foram: 2,48, 1,23 e 0,30, respectivamente. Conclusöes: Os desinfetantes de uso domiciliar a base de compostos de amônio quaternário säo passíveis de contaminaçäo por bactérias. As CIMs do cloreto de benzalcônio para as bactérias contaminantes estavam abaixo das concentraçöes do princípio ativo presente nos desinfetantes, indicando que a tolerância ao biocida näo é estável, podendo ser perdida com o cultivo das bactérias em meios de cultura sem o biocida