Susceptibility of cephalothin-resistant gram-negative bacilli to piperacillin, cefuroxime, and other selected antibiotics

Piperacillin was more consistently active than tobramycin, carbenicillin, moxalactam, or _eftriaxone against strains of Pseudomonas aeruginosa isolated from blood cultures and against multidrug-resistant strains. Moxalactam and ceftriaxone were more consistently active than tobramycin, carbenicillin, or piperacillin against multidrug-resistant Enterobacteriaceae. Synergy between P-lactam antibiotics and tobramycin was frequently observed against strains of P. aeruginosa isolated from blood cultures but not against multidrug-resistant organisms. Piperacillin plus tobramycin was the most active antibiotic combination against P. aeruginosa. Moxalactam plus tobramycin and ceftriaxone plus tobramycin were the most active antibiotic combinations against Enterobacteriaceae.Penicillin-aminoglycoside and cephalosporinaminoglycoside combinations are frequently synergistic against gram-negative enteric bacilli and are commonly used for the treatment of serious infections caused by those organisms (7). A number of new P-lactam antibiotics have been developed which have greater potencies and broader antibacterial spectra than the older penicillins and cephalosporins (3). Combined with an aminoglycoside, they might provide improved therapeutic regimens for the treatment of infections caused by gram-negative organisms which are relatively resistant to the older antibiotics.In this study, the in vitro activities of three new 3-lactam antibiotics, piperacillin (5) colony-forming units per ml were used (4). The ranges of concentrations tested were 0.25 to 256 p.g/ml for 3-lactam antibiotics and 0.25 to 16 ,ug/ ml for tobramycin. The MICs for defining susceptibility were as follows: carbenicillin, s128 ,zg/ml; piperacillin, c64 p.g/ml; moxalactam, <16 F.g/ml; ceftriaxone, 516 ,ug/ml; and tobramycin, c4 Fg/ml. Antibiotics were considered synergistic when there was a fourfold or greater reduction in the MICs of both drugs in the combination compared with the MICs of individual drugs. Antibiotics were considered antagonistic when there was a fourfold or greater increase in the MICs of both drugs or when the addition of an antibiotic with no activity (within the range of concentrations tested) increased the MIC of the other antibiotic by fourfold or more. Results not meeting the criteria for synergy or antagonism were considered indifferent if endpoints were within the ranges of concentrations tested; they were considered indeterminate if they were not within those ranges.The observed antibiotic susceptibilities are shown in Table 1

“…Previous reports have also shown that moxalactam (2) and ceftriaxone (12) but not piperacillin (6,10) …”

mentioning

confidence: 90%

Comparative in vitro activities of beta-lactam-tobramycin combinations against Pseudomonas aeruginosa and multidrug-resistant gram-negative enteric bacilli

Fass¹

1982

“…At a concentration of 12.5 jig/ml, 83% of the isolates were inhibited with PIP, compared to 4 and 2% with TIC and CARB, respectively. A concentration of -200 ,ug of CARB or TIC per ml was required to inhibit 14 isolates, 13 of which were inhibited by PIP at a concentration of at least 25 ,ug/ml.…”

mentioning

confidence: 93%

“…Piperacillin (T-1220) (PIP) is a new semisynthetic derivative of aminobenzyl-penicillin with a broad spectrum of antimicrobial activity, which particularly is more active than either carbenicillin (CARB) or ticarcillin (TIC) against Pseudomonas aeruginosa (3)(4)(5)(6)(7). In the study reported here, the in vitro activities of PIP, CARB, and TIC in combination with gentamicin (GM), tobramycin (TM), and amikacin (AM) against 54 isolates of P. aeruginosa were compared.…”

mentioning

confidence: 99%

Analysis of the Interactions Between Piperacillin, Ticarcillin, or Carbenicillin and Aminoglycoside Antibiotics

Chanbusarakum

Murray

1978

“…830,1979). In vitro and in vivo studies demonstrate that piperacilHin has a broad spectrum of activity (5,7,12,13). It is effective against most gram-positive and gram-negative organisms, including anerobes.…”

mentioning

confidence: 99%

Piperacillin pharmacokinetics in subjects with chronic renal failure

Thompson¹,

Russo²,

Matsen³

et al. 1981

The pharmnacokinetic parameters of piperacillin sodium were studied in eight volunteer subjects with chronic renal failure. Subjects were given a single 30-min intravenous infusion of 70 mg/kg (lean body weight) on their off-dialysis day. Blood was drawn from the contralateral arm at 15 and 30 min and 1, 3, 6, 9, and 12 h from the start of the infusion. Kinetic parameters were determined during the elimination phase with a one-compartment open model for linear kinetics. The following pharmacokinetic parameters (mean ± standard deviation) were determined for the eight subjects: elimination half-life = 3.33 + 0.99 h, elimination rate constant = 0.22 ± 0.06 h-', apparent volume of distribution = 0.18 ± 0.05 liters per kg, and total body clearance = 0.041 ± 0.019 liters per kg/h. The mean peak serum concentration was 372 ± 125 ,ug/ml, and mean trough at 12 h was 39 + 27 ,ug/ml. A dose of 70 mg/kg (lean body weight) or a dose of 4 g appears to provide adequate serum concentrations against susceptible organisms for a 12-h interval. No adverse reactions were noted in any subject throughout the study. Piperacillin has been shown to be effective in the treatment of many serious infections (14; J.