Daley D, Mulgrave L, Munro R, Neville S, Smith H, Dimech W
Department of Microbiology and Infectious Diseases, Liverpool Hospital, NSW.
Pathology. 1996 May;28(2):167-72. doi: 10.1080/00313029600169813.
Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.
他唑巴坦是一种新型的、不可逆的细菌β-内酰胺酶抑制剂，可抑制葡萄球菌的β-内酰胺酶、在大肠杆菌和克雷伯菌属中发现的TEM和SHV型质粒介导的β-内酰胺酶以及诸如拟杆菌属等厌氧菌的β-内酰胺酶。它与广谱脲基青霉素哌拉西林联合使用，有望提高哌拉西林对葡萄球菌、产生TEM和SHVβ-内酰胺酶的革兰氏阴性菌以及厌氧菌的活性。测定了1952株引起严重感染的革兰氏阳性和阴性细菌患者分离株的哌拉西林/他唑巴坦最低抑菌浓度（MIC），并与头孢噻肟、头孢他啶、环丙沙星、亚胺培南、替卡西林/克拉维酸的MIC值进行比较。MIC通过琼脂稀释法测定（NCCLS 1990年和1992年）。哌拉西林/他唑巴坦对甲氧西林敏感葡萄球菌、肺炎链球菌、流感嗜血杆菌、肠球菌以及脆弱拟杆菌属菌群具有优异的活性。它对大多数测试的肠杆菌科细菌和铜绿假单胞菌分离株也有活性。它对产超广谱β-内酰胺酶（ESBL）的克雷伯菌属以及一些产高水平TEM和SHVβ-内酰胺酶的大肠杆菌和克雷伯菌属无活性。对能够产生染色体介导β-内酰胺酶的革兰氏阴性菌活性良好，因为在大多数测试的细菌中，这些酶的诱导量不足以导致抗生素耐药。然而，一些肠杆菌属是去阻遏高产突变体；这些分离株对哌拉西林/他唑巴坦耐药，因为他唑巴坦不抑制这些I类β-内酰胺酶。对于革兰氏阴性杆菌，其活性优于替卡西林/克拉维酸。亚胺培南是对产ESBL的克雷伯菌属活性最强的药物。哌拉西林/他唑巴坦在体外具有合适的活性谱，表明可用于单一疗法治疗混合性厌氧菌感染、混合性呼吸道感染如吸入性肺炎，并且与氨基糖苷类药物联合使用，可为免疫抑制患者发热性疾病提供革兰氏阳性菌和革兰氏阴性菌的覆盖。
