Studies to optimize the in vitro testing of piperacillin combined with tazobactam (YTR 830). 1989

R N Jones, and A L Barry
Clinical Microbiology Institute, Tualatin, Oregon.

The combination of piperacillin and the beta-lactamase inhibitor tazobactam (formerly YTR 830) was studied to determine optimal disk concentrations and dilution testing conditions. In addition, the potency of the combination was compared to that of piperacillin alone. The spectrum of piperacillin was greatly expanded by the addition to tazobactam principally against beta-lactamase producing strains of Haemophilus influenzae, Escherichia coli, Morganella morganii, Proteus vulgaris, Providencia stuartii, Shigella spp., Neisseria gonorrhoeae, and Staphylococcus spp. Tazobactam was active alone against Branhamella catarrhalis (minimum inhibitory concentration [MIC] 50, less than or equal to 1 microgram/ml), gonococci (MIC 50, 0.5-4 micrograms/ml), and N. meningitidis (MIC 50, less than or equal to 1 microgram/ml). Studies with beta-lactamase-producing type strains showed tazobactam to have high affinity for plasmid-mediated enzymes (TEM-1 and 2, SHV-1, HMS-1, and some CARB or OXA types) and not chromosomal beta-lactamases. Piperacillin/tazobactam inhibited 93% of fluoro-quinolone resistant strains at less than or equal to 64/8 micrograms/ml but failed to suppress the growth of 15 strains producing stably depressed cephalosporinases. Comparisons of piperacillin/tazobactam results determined with 100/10-, 100/20-, and 100/30-micrograms disks established the 100/10-micrograms disk as most usable. Among five different MIC combinations the ratio of eight parts piperacillin to one part tazobactam or fixed concentration tests at greater than or equal to 4 micrograms tazobactam/ml were preferred, each producing very low occurrences (less than or equal to 1.6%) of false-resistance or -susceptibility when compared to disk test results. MICs determined by agar and broth microdilution methods were essentially the same. The recommended breakpoints for piperacillin/tazobactam MICs were identical to those now found in the NCCLS susceptibility testing standards with the following exceptions: (1) for tests with H. influenzae and Staphylococcus spp.--susceptible at greater than or equal to 21 mm (MIC less than or equal to 16/2 micrograms/ml) and resistant less than or equal to 20 mm (MIC less or equal to 32/4 micrograms/ml); and (2) all remaining nonspeudomonas isolates would be interpreted by the NCCLS piperacillin enteric bacilli susceptibility criteria. This newer beta-lactamase inhibitor combination appears to be worthy of further in vivo trials guided by these or similar tentative in vitro susceptibility testing parameters.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009345 Neisseria meningitidis A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Diplokokkus intracellularis meningitidis,Meningococcus,Micrococcus intracellularis,Micrococcus meningitidis,Micrococcus meningitidis cerebrospinalis,Neisseria weichselbaumii
D010397 Penicillanic Acid A building block of penicillin, devoid of significant antibacterial activity. (From Merck Index, 11th ed) Acid, Penicillanic
D010878 Piperacillin Semisynthetic, broad-spectrum, AMPICILLIN derived ureidopenicillin antibiotic proposed for PSEUDOMONAS infections. It is also used in combination with other antibiotics. AB-Piperacillin,Cl-227193,Pipcil,Pipera-Hameln,Piperacillin Curasan,Piperacillin Fresenius,Piperacillin Hexal,Piperacillin Monosodium Salt,Piperacillin Sodium,Piperacillin-Ratiopharm,Pipercillin,Pipracil,Pipril,T-1220,T1220,AB Piperacillin,Cl 227193,Cl227193,Curasan, Piperacillin,Monosodium Salt, Piperacillin,Pipera Hameln,Piperacillin Ratiopharm,Salt, Piperacillin Monosodium,Sodium, Piperacillin,T 1220
D011815 R Factors A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation. R Factor,R Plasmid,R Plasmids,Resistance Factor,Resistance Factors,Factor, R,Factor, Resistance,Factors, R,Factors, Resistance,Plasmid, R,Plasmids, R
D001936 Moraxella catarrhalis Gram-negative aerobic cocci of low virulence that colonize the nasopharynx and occasionally cause MENINGITIS; BACTEREMIA; EMPYEMA; PERICARDITIS; and PNEUMONIA. Branhamella catarrhalis,Mikrokkokus catarrhalis,Moraxella (Branhamella) catarrhalis
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D004755 Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Coliform Bacilli,Enterobacteria,Ewingella,Leclercia,Paracolobactrum,Sodalis
D006090 Gram-Negative Bacteria Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. Gram Negative Bacteria

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