Okereke C, Dudley M N
Anti-infective Pharmacology Research Unit, University of Rhode Island College of Pharmacy and Brown University Medical School, Roger Williams Medical Center, Providence 02908, USA.
J Antimicrob Chemother. 1998 Jun;41 Suppl D:43-9. doi: 10.1093/jac/41.suppl_4.43.
Morbidity and mortality in febrile neutropenic patients result mainly from complications attributable to infectious diseases. Both Gram-negative and Gram-positive bacterial infections have been implicated. The use of antibiotics in combating bacterial infections has been hampered by production by many bacterial pathogens of beta-lactamases that render them resistant to beta-lactam antibiotics. Since susceptibility to the beta-lactam appears crucial in attaining a clinical response in Gram-negative bacteraemia in febrile neutropenic patients, regimens that inhibit the activity of beta-lactamases are desirable. Although many beta-lactamase inhibitors, such as tazobactam, can result in irreversible inhibition of bacterial beta-lactamase in vitro, careful selection of dosage, as well as testing in models of infection mimicking that in patients, is required. Experimental studies in in-vitro models of infection that mimic conditions of absent host response, show that tazobactam restores the activity of piperacillin against beta-lactamase-producing bacteria. Optimal dosage regimens of beta-lactamase inhibitors will provide mean concentrations of beta-lactamase inhibitor at or above those used in in-vitro testing.
