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At least 19 recordsLinked to original sources
PubMed1990

Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers.

beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although beta-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcillin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms.

Amoxicillin↗
PubMed1978

Combined activitiy of clavulanic acid and ticarcillin against ticarcillin-resistant, gram-negative bacilli.

Fifty-one clinical isolates of ticarcillin-resistant, gram-negative bacilli were tested for susceptibility to combinations of ticarcillin and clavulanic acid (BRL 14151), a potent beta-lactamase inhibitor. Minimal inhibitory concentrations (MICs) were measured by a microdilution method, and minimal bactericidal concentrations for selected strains were measured by the broth dilution method. Ticarcillin MICs were >/=128 mug/ml for all and >/=512 mug/ml for 38 (75%) of the strains. Thirty-nine strains of Enterobacteriaceae tested included Escherichia coli (14), Klebsiella pneumoniae (16), Citrobacter sp. (3), Enterobacter sp. (3), Salmonella enteritidis (1), Serratia marcescens (1), and Proteus mirabilis (1). Ticarcillin MICs for 34 strains (88%) were lowered at least threefold by the addition of 1.0 mug of clavulanic acid per ml. Against 33 strains (85%), the MICs were 64 mug or less per ml in the presence of 5 mug of clavulanic acid per ml. In contrast, the MICs for seven of eight strains of Pseudomonas aeruginosa were unaffected by the addition of up to 10 mug of clavulanic acid per ml. Ticarcillin with 5 mug of clavulanic acid per ml was bactericidal against ticarcillin-resistant (MIC >/= 2,048 mug/ml) E. coli, K. pneumoniae, Enterobacter, and P. mirabilis.

Anti-Bacterial Agents↗
PubMed1992

Ticarcillin and ticarcillin-clavulanic acid susceptibility tests: error rates for disk tests with consecutively isolated members of the family Enterobacteriaceae.

A five-laboratory coordinated study was undertaken to determine whether ticarcillin and ticarcillin-clavulanic acid disk susceptibility tests could accurately detect resistance among enteric bacilli. Each facility performed disk tests and broth microdilution susceptibility tests with reagents distributed from a common source, and appropriate controls were included in order to ensure methodologic uniformity. Each institution tested 500 consecutively isolated enteric bacilli against ticarcillin and ticarcillin-clavulanic acid. The prevalence of discrepancies between disk tests and dilution tests with 2,435 unselected enteric bacilli provided a valid estimate of the true error rate for tests with the two disks. The current interpretive criteria for susceptibility tests with ticarcillin and ticarcillin-clavulanic acid disks were found to be reliable; i.e., there were major or very major discrepancies between MIC categories and disk test results for less than 1% of all strains and minor discrepancies for only 5 to 10%. Even lower error rates would occur if the zone size-interpretive criteria were modified, but at this time it is difficult to determine whether the practical problems created by making such changes can be justified by the magnitude of the problem that is being resolved.

Clavulanic Acids↗
PubMed1991

Pharmacokinetics of ticarcillin and ticarcillin-probenecid in sheep.

Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23.

Absorption↗
PubMed1992

In vitro antibacterial activities of ticarcillin alone and ticarcillin plus clavulanic acid against beta-lactamase producing and non-producing microorganisms.

A total of 818 clinical bacterial isolates were tested for the production of beta-lactamase by rapid chromogenic cephalosporin method and for the susceptibility to ticarcillin alone and in combination with clavulanic acid (2 micrograms/mL) by agar dilution method. These included 83 strains of methicillin-sensitive Staphylococcus aureus (MSSA), 31 of methicillin-resistant S. aureus (MRSA), 49 of Neisseria gonorrhoeae, 58 of Haemophilus influenzae, 112 of Escherichia coli, 118 of Klebsiella pneumoniae, 58 of Proteus mirabilis, 30 of Proteus vulgaris, 60 of Serratia marcescens, 113 of Enterobacter cloacae, 60 of Pseudomonas aeruginosa and 46 of Bacteroides fragilis. The results revealed that 46.6% of P. mirabilis, 53.4% of H. influenzae, 57.1% of N. gonorrhoeae, 80% of P. vulgaris, 83.9% of MRSA, 85.6% of MSSA, 87.5% of E. coli, 91.7% of S. marcescens, 95.7% of B. fragilis, 98.2% of E. cloacae, and 100% of K. pneumoniae and P. aeruginosa strains produced beta-lactamase. In general, beta-lactamase nonproducers were more susceptible to ticarcillin than beta-lactamase producers. The ranges of minimum inhibitory concentrations (MICs) of ticarcillin for beta-lactamase nonproducers of MSSA, MRSA, H. influenzae, E. coli, P. vulgaris, S. marcescens, E. cloacae, B. fragilis and beta-lactamase producers of MSSA, H. influenzae strains were all within the in vitro susceptible range. The presence of clavulanic acid resulted in a significant enhancement of the antibacterial activity of ticarcillin against beta-lactamase producers of MRSA, N. gonorrhoeae, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris and B. fragilis strains. Clavulanic acid had no synergistic activity for ticarcillin against S. marcescens, P. aeruginosa and E. cloacae.

Bacteria↗
PubMed1989

Reassessment of susceptibility test interpretive criteria for ticarcillin and ticarcillin-clavulanic acid.

There are at least four different existing or proposed interpretive criteria for the disk diffusion susceptibility testing of ticarcillin and ticarcillin plus clavulanic acid (T/C). To assess these criteria, 570 gram-negative bacillary isolates were tested for susceptibility to ticarcillin and T/C by both disk diffusion and broth microdilution methods. These included 53 strains of the family Enterobacteriaceae selected for ticarcillin resistance and high-level beta-lactamase production. The broth microdilution test results were more influenced by increased beta-lactamase production than were disk diffusion results. In the absence of published data indicating which of the two standardized test methods better predicts clinical response, we conclude that until such data are available the more conservative National Committee for Clinical Laboratory Standards tentative criteria for tests with members of the Enterobacteriaceae are appropriate. Our data do not support the use of separate T/C interpretive criteria for Pseudomonas spp. and members of the Enterobacteriaceae. The appropriateness of different interpretive criteria needs further evaluation.

Anti-Bacterial Agents↗
PubMed1989

Ticarcillin-clavulanate therapy for infections with ticarcillin-resistant microorganisms.

In a prospective study, 46 episodes of serious infection with ticarcillin-resistant microorganisms were treated with the combination ticarcillin disodium and clavulanate potassium (Timentin). Clinical cure was achieved in 35 of the 46 episodes (76%), and microbiologic eradication was achieved in 30 (65%). We found no development of resistance to ticarcillin-clavulanate and observed no serious side effects.

Adult↗
PubMed1975

Empiric therapy for cancer patients: comparative study of ticarcillin-tobramycin, ticarcillin-cephalothin, and cephalothin-tobramycin.

Three combinations of antibiotics (cephalothin-tobramycin, cephalothin-ticarcillin, and ticarcillin-tobramycin) were administered empirically to 186 patients with cancer who were suspected of having a life-threatening infection. In approximately one-half of these patients, gram-negative infection was documented bacteriologically and consisted of septicemia in 50% of these patients. The three antimicrobial regimens were similarly effective and resulted in a favorable clinical response in approximately 55% of the patients. The administration of the cephalothin-tobramycin combination was associated with a significantly higher frequency of nephrotoxicity than that of the other two regimens.

Anti-Bacterial Agents↗
PubMed1979

Pseudomonas aeruginosa keratitis treated with ticarcillin and tobramycin.

A corneal ulcer, infected with Pseudomonas aeruginosa and complicated by conjunctivitis and endophthalmitis, was treated successfully with systemic administration of ticarcillin and topical application of tobramycin. It is unlikely that carbenicillin, to which the organism was much less sensitive, would have attained sufficient tissue levels to control the infection.

Aged↗
PubMed1975

Comparative in vitro activity and clinical pharmacology of ticarcillin and carbenicillin.

The in vitro activity and human pharmacology of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared. There has been no increase in resistance to ticarcillin of Pseudomonas strains over the past 5 years, but resistance of indole-positive Proteus and Serratia strains has been documented. After intramuscular (i.m.) injection of 1 g of ticarcillin, mean peak levels occurred at 1 h (26.9 mug/ml) with a decline over 6 h (6.8 mug/ml). Serum half-life was 84 min. Dilution of ticarcillin lidocaine reduced pain on i.m. injection but did not alter serum levels. Blood levels after 1 g i.m. are adequate to treat infections produced by Escherichia coli, Proteus mirabilis, and some Enterobacter, but not Pseudomonas. After rapid intravenous infusion of 3 and 5 g, mean peak serum levels of ticarcillin were slightly lower for 1 h than those achieved with carbenicillin. Probenecid administered before infusion produced increases in blood levels, half-lives, and volume of distribution. The biological half-life of ticarcillin was 72 min compared to 66 min with carbenicillin. There was a larger volume of distribution for ticarcillin than carbenicillin (15 liters versus 14 liters). The ticarcillin half-life when administered with probenecid was 108 min. Urinary recovery of ticarcillin was 77% against 95% of carbenicillin. However, approximately 10% of ticarcillin is recovered as penicilloic acid so that 95% of an intravenously administered dose is recovered.

Carbenicillin↗
PubMed1991

Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration.

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals. The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.

Age Factors↗
PubMed1989

Simulation of human serum pharmacokinetics of ticarcillin-clavulanic acid and ceftazidime in rabbits, and efficacy against experimental Klebsiella pneumoniae meningitis.

The penetration into cerebrospinal fluid (CSF) and efficacy of ticarcillin-clavulanic acid, ticarcillin alone, and ceftazidime were compared in rabbits with experimentally induced Klebsiella pneumoniae meningitis. The compounds were administered to simulate in rabbit plasma the concentration-versus-time curves observed in humans after 30-min infusions of Timentin (3 g of ticarcillin plus 100 mg of clavulanic acid), ticarcillin (3 g), and ceftazidime (2 g). Single- and multiple-dosing schedules were used. The penetrations of clavulanic acid into CSF (expressed as [area under the concentration-time curve for CSF/area under the curve for plasma] x 100) after the two dosing schedules were 28 and 24.5%, similar to that for ceftazidime (21%; multiple-dosing only) and greater than those for ticarcillin (8.4 and 9.3%). Ticarcillin was ineffective in reducing viable counts in CSF but, in the presence of clavulanic acid, reduced bacterial numbers by approximately 99% at 4 h after a single dose and by 99.99% at 12 h after three doses given at 4-h intervals. Two doses of ceftazidime given 8 h apart were more effective than the three doses of ticarcillin-clavulanic acid, in keeping with the in vitro activities of these compounds against the infecting organism. These results illustrate the ability of clavulanic acid to penetrate the blood-CSF barrier such that concentrations of the inhibitor in CSF potentiate the activity of ticarcillin against the ticarcillin-resistant, beta-lactamase-producing strain of K. pneumoniae.

Animals↗
PubMed1976

Comparative activity in vitro of ticarcillin, BL-P1654, and carbenicillin.

The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, and Pseudomonas aeruginosa. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except S. epidermidis against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for S. aureus: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for S. epidermidis: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for E. coli: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for Klebsiella sp.: >100 for all three drugs; for Enterobacter sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for Proteus sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for P. aeruginosa: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against P. aeruginosa. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 mug/ml.

Bacteria↗
PubMed1979

Effect of time and concentration upon interaction between gentamicin, tobramycin, Netilmicin, or amikacin and carbenicillin or ticarcillin.

An aminoglycoside antibiotic and carbenicillin or ticarcillin are widely used in the treatment of patients with gram-negative bacillus infections. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycosides at two concentrations with carbenicillin or ticarcillin at four concentrations. By linear regression analysis, the inactivation of each aminoglycoside was shown to be directly proportional to the concentration of carbenicillin (P < 0.001). Inactivation was significantly (P < 0.01) greater for gentamicin and tobramycin than for amikacin or netilmicin at all carbenicillin concentrations. At carbenicillin concentrations of 300 and 600 mug/ml, significantly (P < 0.005) less inactivation of amikacin occurred when compared to netilmicin. Ticarcillin produced a significant (P < 0.025) inactivation of gentamicin and tobramycin, with inactivation being directly proportional to ticarcillin concentration. No inactivation of amikacin or netilmicin activity occurred unless the ticarcillin concentration was 600 mug/ml. No significant change in aminoglycoside activity occurred when stored with ticarcillin or carbenicillin at concentrations ranging from 100 to 600 mug/ml at -70 degrees C for 56 days. When an aminoglycoside and carbenicillin or ticarcillin are indicated in patients with renal failure, this study supports the use of ticarcillin with either amikacin or netilmicin.

Amikacin↗
PubMedDate not supplied

Comparative in vitro susceptibilities of 504 bacteremic isolates to ticarcillin plus clavulanic acid and other antimicrobial agents.

A total of 504 clinical bacteremic isolates were tested for susceptibility to ticarcillin-clavulanic acid and 12 other antibiotics. Ticarcillin-clavulanic acid showed superior antibacterial activity compared to penicillin, mezlocillin, piperacillin, ticarcillin, gentamicin, and amikacin against bacteremic isolates of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis. However, ticarcillin-clavulanic acid's activity was inferior to that of vancomycin against methicillin-resistant isolates of S. aureus and S. epidermidis. For Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Providencia stuartii, and lactose nonfermenting aerobic gram-negative bacilli, the activity of ticarcillin-clavulanic acid surpassed that of mezlocillin, piperacillin, and ticarcillin. Of the antimicrobial agents tested, ticarcillin, piperacillin, ceftazidime, and amikacin were the most active antibiotics against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1989

Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate.

The in vitro activities of ticarcillin, piperacillin, clavulanic acid, tazobactam, ticarcillin-clavulanate, and piperacillin-tazobactam against 819 bacterial isolates were compared. The two beta-lactamase inhibitors, clavulanic acid and tazobactam, had little useful antibacterial activity but enhanced the activities of the penicillins against beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and methicillin-susceptible Staphylococcus aureus; all strains were susceptible to both combinations. Both enzyme inhibitors also enhanced the activities of the penicillins against most strains of Escherichia coli, Klebsiella spp., Citrobacter diversus, Proteus spp., Providencia spp., and Bacteroides spp. and against occasional strains of Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Clavulanic acid frequently enhanced the activity of ticarcillin against Xanthomonas maltophilia, and tazobactam frequently enhanced the activity of piperacillin against Morganella morganii. Enhancement was observed primarily with strains relatively resistant to the penicillins. In general, clavulanic acid was more effective than tazobactam in enhancing penicillin activity against Klebsiella spp., C. diversus, X. maltophilia, and Bacteroides spp., whereas tazobactam was more effective against Escherichia coli and Proteeae. There was little or no enhancement of activity against Enterococcus faecalis, Aeromonas hydrophila, Pseudomonas aeruginosa, Pseudomonas cepacia, or Acinetobacter anitratus. Clavulanic acid occasionally antagonized the activity of ticarcillin against ticarcillin-susceptible members of the family Enterobacteriaceae, but those strains were still considered susceptible to the combination. Tazobactam never antagonized the activity of piperacillin. In a direct comparison of the activities of ticarcillin-clavulanate and piperacillin-tazobactam, the two were equally active against H. influenzae, B. catarrhalis, and S. aureus; the latter was more active against E. faecalis. For relatively susceptible strains of members of the family Enterobacteriaceae, neither combination was predictably more active than the other, but relatively resistant strains were generally more susceptible to piperacillin-tazobactam. Piperacillin-tazobactam was more active than ticarcillin-clavulanate against A. hydrophila, P. aeruginosa, and P. cepacia, similar in activity against A. anitratus, and less active against X. maltophilia and Bacteroides spp.

Anti-Bacterial Agents↗
PubMed1975

Study of the effects of ticarcillin on blood coagulation and platelet function.

Ticarcillin is a new semisynthetic penicillin similar to carbenicillin. Since carbenicillin has been shown to inhibit platelet function to such an extent that bleeding may accompany its use, an investigation of the effects of ticarcillin on hemostasis was made. The drug was administered to 17 human volunteers for periods of 3 to 10 days in intravenous doses of 100, 200, or 300 mg/kg per day (7 to 21 g/day). Serial studies of blood coagulation and platelet function indicated that coagulation was unaffected by ticarcillin but that platelet function became defective in all subjects. Abnormal platelet function was evidenced by lengthening of bleeding time (17 of 17 volunteers), depressed adenosine diphosphate-induced platelet aggregation (17 of 17), defective collagen-induced aggregation (15 of 17), and abnormal epinephrine-induced aggregation (10 of 17). Prothrombin consumption, due to reduced platelet procoagulant activity, was significantly decreased with a dose of 300 mg/kg per day. Comparison of results from this study with those from an earlier carbenicillin study revealed that ticarcillin at 300 mg/kg per day produces the same defects in hemostasis as does carbenicillin at 300 mg/kg per day, but that lower doses (100 or 200 mg/kg per day) of ticarcillin result in only a mild defect in platelet function. If the effective dose of ticarcillin is proven to be lower than the doses of carbenicillin currently employed for treatment of certain gram-negative infections, bleeding should not be a frequent complication of ticarcillin administration, when the drug is given to patients with normal renal function.

Blood Coagulation↗