In Vitro Activity of Furazlocillin (Bay k 4999) Compared with Those of Mezlocillin, Piperacillin, and Standard Beta-Lactam Antibiotics

The induction of ,-lactamase was studied in a strain of Enterobacter cloacae. A wide variety of P-lactam compounds were found to induce ,-lactamase in this organism, and the degree of induction was directly related to the stability of the inducer to degradation by the enzyme. The kinetics of the induction process were consistent with a system normally under repressor control, suggesting a direct interaction of the P-lactam compound with a repressor protein in the E. cloacae cells. Although these characteristics are common to many inducible systems in gram-negative organisms, the induction of 1-lactamase in this strain was not subject to catabolite repression with glucose and remained unaffected by exogenous cyclic AMP in the culture medium. This suggests that the organization and function of the P-lactamase regulatory genes in E. cloacae are unlike those of other inducible gene systems, such as those composing the well-characterized lactose operon in Escherichia coli.

Section: Methodsmentioning

confidence: 99%

Characterization of beta-lactamase induction in Enterobacter cloacae

Gootz¹,

Sanders²

1983

“…(1,3,5,12). Previous reports indicate that mezlocillin, unlike other anti-Pseudomonas penicillins, retains a high degree of potency against gram-positive organisms and Haemophilus influenzae (5,6,(10)(11)(12). However, most of those studies focused primarily upon groups A and D streptococci and staphylococci, and many did not simultaneously evaluate other penicillins.…”

mentioning

confidence: 98%

Comparative activity of mezlocillin, penicillin, ampicillin, carbenicillin, and ticarcillin against gram-positive bacteria and Haemophilus influenzae

Sanders¹

1981

The in vitro activity of mezlocillin was compared to penicillin G, ampicillin, carbenicillin, and ticarcillin in tests with 195 gram-positive bacteria and 20 Haemophilus influenzae. Against gram-positive isolates excluding enterococci, penicillin was the most active drug, followed by ampicillin, mezlocillin, carbenicillin, and ticarcillin. Ampicillin was the most active of the five drugs against enterococci, whereas mezlocillin was the most active drug against 14 strains of ampicillin-susceptible H. influenzae.Mezlocilhin is a semisynthetic penicillin with a broad spectrum of antibacterial activity that includes Pseudomonas spp. (1,3,5,12

“…Cefotaxime and moxalactam are of particular interest because of their excellent inhibitory ability against all Klebsiella strains studied and because of the probability that they will have a higher therapeutic-to-toxic ratio, as compared with the aminoglycosides. The (4,8). Although no attempt was made to demonstrate beta-lactamase activity in the culture filtrates, other investigators have described this activity for both aerobic organisms (10) and anaerobic organisms (11).…”

Section: Discussionmentioning

confidence: 99%

Klebsiella species: antimicrobial susceptibilities, bactericidal kinetics, and in vitro inactivation of beta-lactam agents

Panwalker¹,

Trager²,

Porembski³

1980

In vitro properties of 19 antimicrobial agents were tested with 56 isolates of Klebsiella spp. The aminoglycosides and the new beta-lactam compounds cefotaxime and moxalactam were the most inhibitory drugs tested. Chloramphenicol, tetracycline, trimethoprim, and trimethoprim-sulfamethoxazole were moderately active, whereas piperacillin, mezlocillin, and furazlocillin were ineffective against 25% of the isolates. Gentamicin was the only agent tested that was uniformly bactericidal in time-kill experiments with drug concentrations of four times the minimal inhibitory concentration. In combination studies with gentamicin, moxalactam and furazlocillin each increased the rate of bacterial killing for three of five isolates as compared with gentamicin alone, whereas chloramphenicol significantly retarded the rate of bacterial killing for the same number of strains. Furazlocillin was completely inactivated after 24 h of incubation with each of five selected strains. The inactivation of moxalactam, cefoxitin, and cephalothin was 36, 56, and 72%, respectively. In all instances in which these four agents were inactivated to levels below the minimal bactericidal concentration, there was accelerated growth after initial inhibition. However, regrowth also occurred in three instances in which drug levels were higher than the minimal bactericidal concentration. Retesting after drug exposure revealed a 4-to 32-fold rise in the minimal inhibitory concentration and minimal bactericidal concentration in two of these isolates.Infections caused by Klebsiella spp. continue to account for a large portion of nosocomial disease with a high rate of morbidity and mortality (6, 7). Aminoglycosides alone and in combination with cephalosporins are frequently prescribed for these serious infections (1). The purpose of this investigation was (i) to study the in vitro activity of aminoglycosides, beta-lactam agents, and other antimicrobial agents against recent clinical isolates of Klebsiellapneumoniae and Klebsiella oxytoca, (ii) to deternine the bactericidal ability of these agents in time-kill experiments, (iii) to examine the rate of bacterial killing of gentamicin alone and in combination with other antimicrobial agents, and (iv) to deternine the rates of inactivation of the betalactam compounds by Klebsiella spp. during the time-kill experiments. MATERIALS AND METHODSAntimicrobial agents. A total of 19 antimicrobial agents were studied. The aminoglycosides used were streptomycin, gentamicin, tobramycin, amikacin, and netilmicin. The beta-lactam compounds included cephalothin, cefazolin, cephapirin, cefoxitin, cefaman-