Disease relevance of Tazobactam

• Potential for selection of antibiotic-resistant gram-negative bacteria during periods of homogeneous exposure increased from cefpirome to piperacillin/tazobactam to levofloxacin [1].
• Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species [2].
• Mechanism of suppression of piperacillin resistance in enterobacteria by tazobactam [3].
• Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group [4].
• Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia [4].

High impact information on Tazobactam

• After acylation of tazobactam by Ser(130) --> Gly, inactivation proceeds independent of any additional covalent interactions [5].
• In TEM-1 and SHV-1, the common class A beta-lactamases, alterations at Ser-130 confer resistance to inactivation by the beta-lactamase inhibitors, clavulanic acid, and tazobactam [6].
• Mechanism of inhibition of the class A beta -lactamases PC1 and TEM-1 by tazobactam. Observation of reaction products by electrospray ionization mass spectrometry [7].
• The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction [8].
• It has a narrow-spectrum hydrolysis of beta-lactams and is strongly inhibited by clavulanic acid and sulbactam and, to a lesser extent, by tazobactam [9].

Chemical compound and disease context of Tazobactam

• The beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam have intrinsic activity against Acinetobacter strains [10].
• Piperacillin/tazobactam in combination with an aminoglycoside was effective in the empirical treatment of fever in patients with neutropenia and compared favourably with ceftazidime in combination with an aminoglycoside, although second-line therapy with a glycopeptide antibiotic may be indicated in unresponsive episodes [11].
• The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages [12].
• The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against Capnocytophaga, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection [13].
• In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP) [14].

Biological context of Tazobactam

• Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of hydrocephalic patients [15].
• The crystal structure provides a rationale for this finding since only tazobactam is able to form favorable intra- and intermolecular interactions in the active site that stabilize this trans-enamine intermediate [16].
• OXA-29 was inhibited by BRL 42715 (50% inhibitory concentration [IC(50)], 0.44 microM) and by tazobactam (IC(50), 3.2 microM), but not by clavulanate [17].
• The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF [18].
• For tazobactam, the ratio of the area under the concentration-time curve (AUC) in CSF to the AUC in serum was approximately three times as high as that for piperacillin (medians, 0.106 versus 0.034) [15].

Anatomical context of Tazobactam

• From a therapeutic viewpoint, given the concentrations of tazobactam recorded in bile fluid and tissue, the addition of this beta-lactamase inhibitor to piperacillin therapy might be of interest in the management of biliary tract infections, mostly in patients at risk of mixed aerobic-anaerobic infections due to beta-lactamase-producing organisms [19].
• The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone [18].
• The mean concentration of tazobactam in the investigated gastrointestinal tissues (appendix, proximal and distal mucosa) exceeded levels in plasma after 1 h, while piperacillin showed a mean penetration into these tissues of 43 and 53% [20].
• Inflammatory exudate penetration was rapid, and the mean maximum levels of tazobactam attained were 6.4 and 11.3 micrograms/ml when it was given alone or with piperacillin, respectively (P less than 0.06) [21].
• The concentration ratios of piperacillin/tazobactam were 9.4 +/- 1.8 in cancellous bone tissue and 8.0 +/- 2.2 in cortical bone tissue, which were close to the 8:1 ratio of drugs administered [22].

Associations of Tazobactam with other chemical compounds

• Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography [8].
• The efficacy and safety of piperacillin plus tazobactam and of imipenem plus cilastatin were compared in an open randomized multicentre study [23].
• MIC patterns and hydrolysis assays suggested that they hyperproduced AmpC beta-lactamase, but synergy between ceftazidime and tazobactam was greater than between ceftazidime and Ro 48-1256, whereas the converse pattern is typical of AmpC hyperproducers [24].
• Ceftriaxone, in combination with tazobactam, given in one dose immediately after infection showed a significant reduction in bacterial count [25].
• The plasmid-encoded ampicillin resistance was mediated by a penicillinase of molecular weight 49,000, and pI 8.45 which was inhibited by clavulanate (IC50 = 0.1 mg/L) and tazobactam (IC50 = 0.42 mg/L) but not by parachloromercuribenzoate or EDTA [26].

Gene context of Tazobactam

• Tazobactam also had no effect on the accumulation of a key intermediate in the AmpC beta-lactamase induction pathway, 1,6-anhydromurotripeptide, in an ampD mutant strain of E. coli [3].
• Because of the need for control of beta-lactamase-mediated resistance and the recent development of tazobactam, the author has examined the inhibitors of various beta-lactamases for their effectiveness [27].
• Although the calvulanic acid combination was more potent, tazobactam was effective for a similar spectrum of resistant gram-negative clinical isolates containing beta-lactamase [28].
• Organisms with type C beta-lactamase were less susceptible than those with type A enzyme to piperacillin/tazobactam and amoxycillin/tazobactam in disc and MIC tests, and to co-amoxiclav in disc tests only [29].
• Clavulanate and penam sulphones (sulbactam and tazobactam) were more active against TEM-1 and OXA-1, but were less active against TEM-3 and cephalosporinase (Case) than SYN-1012 [30].

Analytical, diagnostic and therapeutic context of Tazobactam

• The concentrations of tazobactam achieved are sufficient to exert anti-beta-lactamase activity and supportive of clinical trials involving bone and joint infections, including those caused by beta-lactamase-producing pathogens [22].
• Consistent with minimum inhibitory concentrations that show resistance to beta-lactam beta-lactamase inhibitors, the apparent Ki values, turnover numbers and partition ratios (kcat/kinact) for the mechanism-based inactivators clavulanate, sulbactam and tazobactam are increased [31].
• The pharmacokinetics of tazobactam and piperacillin in plasma and different tissues after a 30-min intravenous infusion of 4 g of piperacillin and 0.5 g of tazobactam were investigated in 18 patients who underwent elective colorectal surgery [20].
• Two species resulting from the reaction of the SHV-1 class A beta-lactamase with the sulfone inhibitor tazobactam have been trapped at 100 K and mapped by X-ray crystallography at 2.0 A resolution [32].
• Comparative activity of piperacillin/tazobactam against 5625 isolates from hospitalised patients. Multicentre Study Group [33].

References