Tazobactam

Tazobactam, a penicillanic acid sulfone derivative, is a drug that inhibits the action of bacterial beta-lactamases especially those belonging to the SHV-1 and 

TEM groups. Tazobactam is beta-lactamase inhibitor that helps piperacillin work better. Recently, its combination with ceftolozane and metronidazole was found to be a safe and effective new antimicrobial combination approved for the treatment of complicated gastrointestinal and urinary-tract infection [129]. 

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Penicillins and other /3-lactam antibiotics (see the Focus On in this chapter) typically develop a resistance to bacteria due to bacterial synthesis of /Mactamase enzymes. Tazobactam, however, is able to inhibit the activity of the /3-lactamase by trapping it, thereby preventing resistance from developing. 

Tautomer, 264, 842 Tautomerism, 842 Tazobactam, 836 Teflon, structure and uses of, 242 Template strand (DNA), 1108 Tercphthalic acid, synthesis of, 576-577... 

Inactivators of class A (3-lactamases (clavulanate, sulbactam, tazobactam) are themselves (3-lactams and act as suicide substrates. They can be used in... 

Augmentin-eombination of amoxicillin and clavulanic add Hmentin-combination of ticardllin and davulanicaad Unasyn-eombination of ampidllin and sulbactam Zosyn-eombination of piperadllin and tazobactam... 

Figure 5.21 Structure of tazobactam. Reprinted from Biochim. Biophys. Acta, 1547, Bonomo, R. A., Liu, J., Chen, Y., Ng, L., Hujer, A. M. and Anderson, V. E., Inactivation of CMY-2 /3-lactamase by tazobactam initial mass spectroscopic characterization , 196-205, Copyright (2001), with permission from Elsevier Science.

Fig. 5.6 A, Nocardicin A B, 3-aminomonobactamic acid (3-AMA) C, aztreonam D, penicillanic acid sulphone (sodium salt) E, / -bromopenicillamc acid (sodium salt) F, tazobactam G, sulbactam.

Tazobactam (Tig. 5.6F) is a penicillanic acid sulphone derivative marketed as a combination with piperacillin. Alone it has poor intrinsic antibacterial activity but is comparable to clavulanic acid in inhibiting /J-lactamase activity. 

Sulbactam (Tig. 5.6G) is a semisynthetic 6-desaminopenicillin sulphone stmcturally related to tazobactam. Not only is it an effective inhibitor of many /Mactamases but it is also active alone against certain Gram-negative bacteria. It is used in combination with ampicillin for clinical use. 

Piperacillin-tazobactam, cefepime, imipenem, or meropenem plus either. 

Piperacillin/tazobactam 3.375 g every 6 hours Avoid if allergic to penicillin... 

Suppose a surgeon requested piperacillin/tazobactam 3.375 g IV every 6 hours for this patient. Would this be a reasonable choice Why or why not ... 

The patient was admitted to the hospital with a presumptive diagnosis of health care-associated pneumonia (based on the recent hospitalization). He received intravenous hydration with normal saline, 5 L oxygen via face mask, an insulin infusion to control his glucose, and empirical antimicrobial therapy with piperacillin-tazobactam 2.25 g intravenously every 6 hours and vancomycin 1 g intravenously every 24 hours. All other medications are continued with the exception of the diabetes medications. 

Injection drug use MSSA GAS Gram-negatives Anaerobes CA-MRSAd Amoxicillin-clavulanate 500 mg every 8 hours Fluoroquinolone + clindamycin 300 mg every 6 hours TMP-SMX DS 1-2 tabs every 12 hours + clindamycin 300 mg every 6 hours Ampicillin-sulbactam 3 g every 6 hours Piperacillin-tazobactam 3.375 g every 6 hours Ceftriaxone 1 g daily + clindamycin 600 mg every 8 hours Ertapenem 1 g daily... 

Piperacillin-tazobactam 3.375-4.5 g IV every 6 hours Imipenem-cilastatin 500 mg IV every 6 hours Ceftazidime 2 g IV + clindamycin 600 mg IV every 8 hours... 

Ampicillin, ampicil I in-sulbactam, ticarci 11 i n-clavu lanate, piperaci 11 in piperaci 11 i n-tazobactam Cephalosporins... 

Insufficiency SO years) peripheral neuropathy Enterobacteriaceae, P. aeruginosa, Enterococcus spp., anaerobes Vancomycin PLUS (1) piperacillin/tazobactam (2) imipenem/cilastatin or meropenem (3) cefepime or ceftazidime and clindamycin or metronidazole (4) ciprofloxacin or levofloxacin and clindamycin or metronidazole... 

Intra-abdominal Ampicillin-sulbactam OR Fluoroquinolone + metronidazole Piperacillin-tazobactam OR Imipenem or meropenem OR Cefepime plus metronidazole OR Ciprofloxacin or levofloxacin plus metronidazole... 

Treatment for septic patients with hospital-acquired, ventilator-acquired, and health care-associated pneumonia is dependent on risk factors for multi-drug resistant (MDR) organisms (Fig. 79-2). Recommended treatment for patients with no MDR risk factors are third-generation cephalosporins, fluoroquinolones, ampicillin-sulbactam, or ertapenem (see Table 79-3).35 Recommended treatment for patients with MDR risk factors are P-lactam/p-lactamase inhibitors (piperacillin-tazobactam), antipseudomonal cephalosporin, or carbapenem, plus an aminoglycoside, plus vancomycin or linezolid (see Table 79-3).35 If an aminoglycoside is undesirable, a antipseudomonal fluoroquinolone may be utilized with a P-lactam/p-lactamase inhibitor. 

A 43-year-old male in the surgical ICU after exploratory laparotomy following a motor vehicle accident develops fever that is unresponsive to broad-spectrum antibacterial therapy (piperacillin-tazobactam 3.75 g every 6 hours, gentamicin 120 mg every 8 hours, and vancomycin 1 g every 12 hours). The patient has a central venous catheter and a Foley catheter. Blood cultures are negative at the time, but the patient has yeast growing in the sputum and urine. Laboratory studies reveal a white blood cell count of 11,300 cells/mm3 (11.3 x 109/L). 

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