Piperacillin toxicity

The more basic interactions between piperacillin and methotrexate and its major metabolite 7-hydroxymetho-trexate have been stndied in rabbits (255). The interaction was mainly cansed by rednced renal clearance of both methotrexate and its metabolite. The anthors concluded that renal function in patients taking this combination should be monitored, with adequate fluid intake, especially in elderly patients, because dehydration may accelerate the occurrence of toxicity. 

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 -I- tazobactam and amikacin (10). 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 tei-coplanin-treated patients, toxicity (renal, liver, and ear toxicity, diarrhea, phlebitis) was also similar. 

Results from animal studies indicate that while furosemide enhanced cephaloridine nephrotoxicity no increased renal toxicity was observed by combining of piperacillin with furosemide [142]. Latamoxef and flo-moxef may decrease nephrotoxicity of vancomycin by inhibiting its uptake into the kidney [146,147]. The results of a retrospective study including renal transplant patients indicate that aztreonam can be safely administered with cyclosporine [148]. Combination therapy with ampicillin/aztreonam in neonates showed a lower renal toxicity than in the group with concurrent administration of oxacillin/ amikacin [149]. 

It is incumbent on health professionals to avoid toxic drugs whenever possible. Antibiotics associated with CNS toxicities, usually when not dose-adjusted for renal function, include penicillins, cephalosporins, quinolones, and imipenem. Hematologic toxicities generally are manifested with prolonged use of nafcillin (neutropenia), piperacillin (platelet dysfunction), cefotetan (hypoprothrombinemia), chloramphenicol (bone marrow suppression, both idiosyncratic and dose-related toxicity), and trimethoprim (megaloblastic anemia). Reversible nephrotoxicity classically is associated with aminoglycosides... 

ApparerU toxic effects include bone marrow depression, granulocytopenia, and hepatitis the latter is rare but is seen most commonly following the administration of oxacillin and nafcillin. Penicillin G, carbenicillin, piperacillin, or ticarcillin has been associated with impaired hemostasis due to defective platelet aggregation. 

The nephrotoxic effects of gentamicin and tohramycin ate well documented. The reason why piperacillin but not carbenicillin or ticarcillin should increase the risk of nephrotoxicity is not clear. One suggestion is that sodium loading may protect the kidney iiom tohramycin toxicity and piperacillin has only 40% as much sodium as ticarcillin. ... 

Reduced clearance and acute methotrexate toxicity has been attributed to the concurrent use of various penicillins (amoxicillin, benzylpenicillin, carbenicillin, dicloxacillin, flucloxacillin, mezlocillin, oxacillin, penicillin, phenoxymethylpenicillin, piperacillin, ticarcillin) in a small number of case reports. 

An 11-year-old girl with T-cell acute lymphoblastic leukaemia received vincristine as part of her chemotherapy regimen. From the first day of therapy, she reported jaw and abdominal pain. On day 17 of chemotherapy, piperacillin/ tazobactam was started for febrile neutropenia and continued until day 45. During this time, the patient experienced progressive constipation and subsequent bowel obstruction, seizures managed with phenobarbital, cholestasis and severe neurologic pain. While the patient received other drugs (i.e. nalbuphine) that could have contributed to the patient s symptoms, the authors hypothesise that a polymorphism involved with the metabolism of piperacillin and vincristine were the main cause of fhe patient s toxicity [49 ]. 

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