Comparative Study of Anti-Pseudomonas Activity of Azlocillin, Mezlocillin, and Ticarcillin

Coppens, Luc; Klastersky, Jean

doi:10.1128/aac.15.3.396

Cited by 41 publications

(12 citation statements)

References 6 publications

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“…However, similar problems existed in the prior study where carbenicillin plus sisomicin were administered at identical intervals. Second, some studies have reported significantly less bactericidal activity for azlocillin against P. aeruginosa compared with that of carbenicillin or ticarcillin (2,8); others have not (1,7). Our own studies demonstrated no differences in the rates of killing for P. aeruginosa by azlocillin or carbenicillin.…”

Section: Resultsmentioning

confidence: 52%

Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa

Norden¹,

Shaffer²

1982

Antimicrob Agents Chemother

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Aziocillin and tobramycin were used alone and in combination in the treatment of chronic osteomyelitis due to Pseudomonas aeruginosa in rabbits. This combination showed in vitro synergy measured by both the checkerboard technique and time-kill curves. A marked inoculum effect was demonstrated in vitro with azlocillin and the infecting strain of P. aeruginosa. The minimal inhibitory concentration of azlocillin, with an inoculum of 105 organisms, was 12.5 ,ug/ml; when the inoculum size was increased to 107 organisms, the minimal inhibitory concentration rose to more than 500 ,ug/ml. In therapeutic trials, the combination of azlocilhin and tobramycin, given for 28 days, was significantly better than either no therapy or azlocillin alone, but was not significantly better than tobramycin alone. Even after 4 weeks of combined therapy with azlocillin and tobramycin, P. aeruginosa was recovered from the bones of 60% of the treated rabbits.A previous study in an experimental model of osteomyelitis caused by Pseudomonas aeruginosa showed that the combination of carbenicillin and sisomicin was significantly more effective (when administered for 4 weeks) than either agent alone (5). However, that combination failed to sterilize the bones of 30% of the rabbits treated, and it was apparent that a more effective regimen would be desirable. Azlocillin and tobramycin were selected for further testing in this experimental model. Tobramycin is as active in vitro as sisomicin against the infecting strain of P. aeruginosa; azlocillin showed considerably greater activity than carbenicillin in initial in vitro testing against the infecting strain of P.aeruginosa. It seemed plausible that azlocillin, either alone or in combination with tobramycin, might be an effective regimen for treatment of experimental osteomyelitis caused by P. aeruginosa. The present study measured the efficacy of azlocillin and tobramycin alone and in combination in this model. This combination, given for 28 days, was more effective than either no therapy or azlocillin alone, but failed to sterilize the bones of 60% of the treated rabbits.MATERIALS AND METHODS Production of osteomyelitis. The technique for production of osteomyelitis has been described previously (5). New Zealand white rabbits (weight 1.5 to 2 kg) received an intramedullary injection into the tibia of sodium morrhuate and 2 x 107 colony-forming units (CFU) of P. aeruginosa (5). The strain used was isolated from a patient with osteomyelitis. It was sensitive to polymyxin, carbenicillin, azlocillin, gentamicin, tobramycin, sisomicin, and amikacin. It was resistant to bacteriolysis when tested with fresh serum from five normal individuals.Determination of MICs. An inoculum (0.5 ml containing either 10' or 107 CFU of P. aeruginosa per ml in Mueller-Hinton broth) was added to 0.5 ml of serial dilutions of antibiotic standards. The mixture was incubated at 37°C for 18 h and then observed for turbidity. The lowest concentration of antibiotic for which no growth was visible was the minimal inhibitory co...

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Section: Resultsmentioning

confidence: 52%

Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa

Norden¹,

Shaffer²

1982

Antimicrob Agents Chemother

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“…aeruginosa. Azlocillin has been reported as being more active than ticarcillin (Coppens and Klastersky, 1979), although other findings suggest the converse (White, Comber and Sutherland, 1980). Cefsulodin has been shown to be more active than either azlocillin or ticarcillin (Zak et al, 1979).…”

Section: Introductionmentioning

confidence: 50%

The response of Pseudomonas aeruginosa to azlocillin, ticarcillin and cefsulodin

Elliott

Greenwood

1983

Journal of Medical Microbiology

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“…In addition, the bactericidal activity of ureidopenicillins against P. aeruginosa has been reported to be much less than that of carbenicillin or ticarcillin (6,7,13,14), although in other studies little or no difference was observed in this respect between the two classes of penicillins (5,15,18).…”

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confidence: 91%

Comparative bactericidal effects of azlocillin and ticarcillin against Pseudomonas aeruginosa

White¹,

Comber²,

Sutherland³

1980

Antimicrob Agents Chemother

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Azlocillin was relatively ineffective against actively growing cultures of Pseudomonas aeruginosa in tests of bacteriolytic and bactericidal activity in which ticarcillin demonstrated pronounced bactericidal effects over a wide range of concentrations. Microscopic observation showed that azlocillin generally induced the formation of filamentous cells of P. aeruginosa which lysed only slowly, but ticarcillin caused the production of spheroplasts and subsequent rapid lysis. During the course of the bactericidal tests, azlocillin was inactivated, presumably by the fi-lactamase produced by P. aeruginosa, and the filamentous cells resumed normal cell division and growth. In contrast, there was no loss of ticarcillin activity, and there was no evidence of resumption of growth of P. aeruginosa in the presence of ticarcillin. These results suggest that the different bactericidal effects demonstrated by azlocillin and ticarcillin against P. aeruginosa are related primarily to dose-related differences in inhibition of cell wall synthesis and secondarily to the instability of azlocillin to pseudomonal /3-lactamase.There are at present two classes of penicillins known to possess significant activity against Pseudomonas aeruginosa. These comprise the a-carboxypenicillins, carbenicillin and ticarcillin, possessing an acidic group in the side chain of the molecule, and the acylaminopenicillins, derivatives of ampicillin or amoxycillin with a basic group in the side chain (12). Examples of the latter group include the two ureidopenicillins, azlocillin and mezlocillin (3,7,8,15), which are available in Europe, and apalcillin (4, 10, 11) and piperacilin. (6,14,17,18), which are in widespread clinical trial.From the results of published studies it is evident that there are pronounced differences between the a-carboxypenicillins and the acylaminopenicillins with regard to the antibacterial effects produced against P. aeruginosa. For instance, the antipseudomonal activity of the latter is greatly influenced by inoculum size (3,6,15), and this has been correlated with instability to the f8-lactamase of P. aeruginosa (2).In addition, the bactericidal activity of ureidopenicillins against P. aeruginosa has been reported to be much less than that of carbenicillin or ticarcillin (6,7,13,14), although in other studies little or no difference was observed in this respect between the two classes of penicil- lins (5, 15, 18).This study was designed to compare the bactericidal effects produced by azlocillin and ticarcillin against P. aeruginosa, as measured by tests of bacteriolytic activity, viable count studies, and observation of the morphological effects produced by the two penicillins.MATERIALS AND METHODS Antibiotics. Azlocillin (sodium) was a laboratory preparation provided by Bayer AG (Leverkusen, Federal Republic of Germany), and ticarcillin (disodium) was laboratory reference standard material (Beecham Pharmaceuticals, Worthing, England).Cultures. P. aeruginosa ATCC 27853 and P. aeruginosa NCTC 10662 are standard laboratory strains ...

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Comparative Study of Anti-Pseudomonas Activity of Azlocillin, Mezlocillin, and Ticarcillin

Cited by 41 publications

References 6 publications

Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa

Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa

The response of Pseudomonas aeruginosa to azlocillin, ticarcillin and cefsulodin

Comparative bactericidal effects of azlocillin and ticarcillin against Pseudomonas aeruginosa

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