Piperacillin-tazobactam dosing

Monotherapy with imipenem 0.5 g IV every 6-8 hours, meropenem 1 g IV every 8 hours, ertapenem 1 g IV every 24 hours, extended-spectrum penicillins with a /3-lactamase inhibitor (piperacillin/tazobactam 4.5 g IV every 6 hours), or tigecycline 100 mg IV as loading dose, then 50 mg IV every 12 hours... 

The indications for penidllin-3-lactamase inhibitor combinations are empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised and immunocompetent patients and treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections. Doses are the same as those used for the single agents except that the recommended dosage of piperacillin in the piperacillin-tazobactam combination is 3 g every 6 hours. Adjustments for renal insufficiency are made based on the penicillin component. 

Piperacillin-Tazobactam (Zesyn) [Anribioric/Extended Spectrum Penicillin, Beta Lactamase Inhibitor] Uses Infxns of skin, bone, resp urinary tract, abd, sepsis Action PCN plus 3-lactamase inhibitor bactericidal i cell wall synth Dose Adults. 3.375-4.5 g IV q6h i in renal insuff Caution [B, M] Contra PCN or 3-lactam sensitivity Disp Powder for inj frozen, premix inj 3.25, 3.375, 4.5 g SE D, HA, insomnia, GI upset, serum sickness-like Rxn, pseudomembranous colitis Interactions T Effects W/ probenecid T effects OF anticoagulants, MTX i effects W/ macrolides, tetracyclines i effects OF OCPs EMS T Effects of anticoagulants monitor for signs of electrolyte disturbances and hypovolemia d/t D such as X- K+ may cause allergic Rxn in pts sensitive to PCN OD May cause N/V/D, resp difficulty, and Szs symptomatic and supportive... 

Ruiz-Irastorza G, Barreiro G, Aguirre C. Reversible bone marrow depression by high-dose piperacillin/tazobactam. Br J Haematol 1996 95(4) 611-12. 

In a randomized, prospective, cost-effectiveness study both teicoplanin and vancomycin were assessed as second-line therapy in 66 neutropenic patients after the failure of empirical treatment with a combination of piperacillin + tazobactam and amikacin (26). The primary success of second-line therapy was equivalent, and the direct total costs were similar. Acquisition costs per dose were in favor of vancomycin, but costs derived from administering vancomycin and serum concentration monitoring led to similar costs for both regimens. With the exception of the red man syndrome, which occurred in 10% of vancomycin-treated patients but none of the teicoplanin-treated patients, toxicity (renal, Uver, and ear toxicity, diarrhea, phlebitis) was also similar. 

The combination of piperacillin and tazobactam does not increase the activity of piperacillin against P. aeruginosa because there is resistance due to either chromosomal P-lactamases or decreased permeability of piperacillin into the periplasmic space. Because the currently recommended dose (3 g piperacillin per 375 mg tazobactam every 4 to 8 hours) is less than the recommended dose of piperacillin when used alone for serious infections (3 to 4 g every 4 to 6 hours), concern has been raised that piperacillin-tazobactam may prove ineffective in the treatment of some P. aeruginosa infections that would have responded to piperacillin. The combination of piperacillin plus tazobactam should be equivalent in antimicrobial spectrum to ticarcillin plus clavulanate. 

An 87-year-old man who was given piperacillin + tazobactam 2 g + 250 mg every 12 hours after hemodialysis developed auditory and visual hallucinations, bizarre behavior, disorientation, and progressive mental confusion 2 hours after the sixth dose. Piperacillin + tazobactam was withdrawn, and he recovered within 6 hours. The serum piperacillin concentration was 56 mg/1. 

PIPERACILLIN SODIUM AND TAZOBACTAM SOD/L/M Administer by IV infusion over 30 minutes. The usual total daily dose for adults is 12 g/1.5 g, given as 3.375 g every 6 hours. 

Reversible bone marrow suppression after high-dose piperacillin-I-tazobactam was seen in an underweight woman and was thought to be a dose-dependent and piperacillin-related effect (10). 

Tazobactam, USP. Tazobactam is a penicillanic acid sulfone that is similar in structure to sulbactam. It is a nioK potent /3-lactamase inhibitor than sulbactam and ha.- 3 slightly broader spectrum of activity than clavulanic acid. Ii has very weak antibacterial activity. Tazobactam is available in fixed-dose, injectable combinations with piperacillin, a broad-spectrum penicillin consisting of an 8 I ratio of pipci- acillin sodium to tazobactam sodium by weight and ma-keted under the trade name Zosyn. The pharmacokineticsprotein bound, experience ven little metabolism, and are excreted in active forms in the urine in high concentrations. 

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