Corso A, Galas M F, Rossi M A
Instituto Nacional de Microbiología Dr. Carlos Malbrán, Buenos Aires, Argentina.
Rev Argent Microbiol. 1996 Jul-Sep;28(3):123-31.
The determination of serum concentrations of antimicrobials with a narrow therapeutic range by microbiological method requires some modifications when the patient is under combined antimicrobial therapy. The methodological conditions for the appraisal of aminoglycosides and vancomycin in the presence of other drugs were evaluated by using strains with selective sensitivity to the antimicrobial to be tested or by the adding crude extracts of beta-lactamases for the inactivation of the beta-lactam antimicrobials. These beta-lactamases were obtained from Enterobacter cloacae P99 (derepressed mutant) cultures for the inactivation of penicillins and first, second and third generation cephalosporins, as well as from Stenotrophomonas (Xanthomonas) maltophilia M 1484 cultures for the hydrolysis of imipenem. The strains allowing vancomycin appraisal and indifferent to the synergic activity of other drugs in the mixture were S. aureus M 2120, when the accompanying antimicrobials were gentamicin, ciprofloxacin or rifampicin, and E. faecalis M 2113, E. avium M 2091 and S. aureus M 2101 when the drugs in the mixture were amikacin, lincomycin or trimethoprim-sulfamethoxazole, respectively. For the appraisal of gentamicin in the presence of vancomycin or fluoroquinolones (ciprofloxacin or norfloxacin), E. coli M 1376 was the most suitable strain, while the use of K. pneumoniae ATCC 10031 was required for the appraisal of amikacin or netilmicin. When rifampicin was the accompanying antimicrobial, E. coli M 1495 turned out more adequate. E. coli M 1462 proved to be more satisfactory for gentamicin, amikacin and netilmicin dosages in samples also containing chloramphenicol, trimethoprim-sulfamethoxazole or tetracycline.
当患者接受联合抗菌治疗时,采用微生物学方法测定治疗窗窄的抗菌药物的血清浓度需要做一些调整。通过使用对被测抗菌药物具有选择性敏感性的菌株,或添加β-内酰胺酶粗提物使β-内酰胺类抗菌药物失活,来评估在其他药物存在的情况下氨基糖苷类和万古霉素的方法学条件。这些β-内酰胺酶分别从阴沟肠杆菌P99(去阻遏突变体)培养物中获得,用于使青霉素及第一、二、三代头孢菌素失活;从嗜麦芽窄食单胞菌(嗜麦芽黄单胞菌)M 1484培养物中获得,用于使亚胺培南水解。当混合使用的其他药物为庆大霉素、环丙沙星或利福平,允许评估万古霉素且对混合物中其他药物的协同活性无影响的菌株是金黄色葡萄球菌M 2120;当混合物中的药物分别为阿米卡星、林可霉素或甲氧苄啶-磺胺甲恶唑时,允许评估万古霉素的菌株是粪肠球菌M 2113、鸟肠球菌M 2091和金黄色葡萄球菌M 2101。对于在万古霉素或氟喹诺酮类药物(环丙沙星或诺氟沙星)存在的情况下评估庆大霉素,大肠杆菌M 1376是最合适的菌株;而评估阿米卡星或奈替米星则需要使用肺炎克雷伯菌ATCC 10031。当伴随使用的抗菌药物为利福平时,大肠杆菌M 1495更适用。对于还含有氯霉素、甲氧苄啶-磺胺甲恶唑或四环素的样品中庆大霉素、阿米卡星和奈替米星的剂量测定,大肠杆菌M 1462被证明更令人满意。