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At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

PubMed1976

Comparison and evaluation of ticarcillin and carbenicillin using disk diffusion methods.

Ticarcillin has proved to be two- to fourfold more active than carbenicillin against most strains of Pseudomonas aeruginosa. Although susceptibility of the Enterobacteriaceae to ticarcillin could be predicted from results obtained with carbenicillin disks, neither the 50-mug nor the 100-mug carbenicillin disk proved suitable for testing susceptibility of P. aeruginosa to ticarcillin. Forty-three percent of Pseudomonas strains judged to be resistant to carbenicillin by the 100-mug carbenicillin disk were susceptible to ticarcillin by agar dilution studies. Results obtained with a 75-mug ticarcillin disk showed excellent correlation between zone size and ticarcillin minimal inhibitory concentration values and produced good discrimination between resistant and susceptible strains of Pseudomonas as determined by agar dilution studies. Using a 75-mug ticarcillin disk, a zone size of 12 to 14 mm was appropriate for designating intermediate susceptibility, and a zone greater than or equal to 15 mm was appropriate for designating susceptible strains of both P. aeruginosa and the Enterobacteriaceae.

Carbenicillin↗

PubMed1975

Ticarcillin vs carbenicillin: clinical pharmacokinetics.

The pharmacokinetic characteristics of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared to those of carbenicillin in 12 healthy volunteers. Following an intravenous infusion of 2 gm in 5 min, there was a lower average serum level for ticarcillin (218 mug/ml) than for carbenicillin (301 mug/ml), but after 2 hr the differences were not significant. The biologic half-life of ticarcillin was slightly longer than that of carbenicillin (72 and 65 min, P smaller than 0.01) and its volume of distribution was larger (15.7 and 12.3 l, P smaller than 0.01). Eighty-six per cent of the dose of ticarcillin and 99 percent of the dose of carbenicillin was recovered in the urine in 24 hr. Similar but much less marked blood level differences were noted with 2 gm, 30-min infusions. An intravenous infusion of 1 gm/hr gave average steady-state blood levels of about 124 mug/ml for both antibiotics. Probenecid, administered 1 hr before the infusion, caused significant and similar increases in blood levels, half-lives, and volumes of distribution of the 2 antibiotics. Protein binding in 100 percent human serum was 50 percent and 65 percent for carbenicillin and ticarcillin, respectively. These relatively small but definite differences in the pharmacokinetics of ticarcillin and carbenicillin are not likely to be of clinical significance.

Carbenicillin↗

PubMed1979

Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer.

A randomized trial of ticarcillin plus gentamicin (group 1), ticarcillin plus amikacin (group 2) and ticarcillin plus netilmicin (group 3) as empiric antibiotic therapy in patients with granulocytopenia and cancer was carried out at the Baltimore Cancer Research Center. The response rate for all infections was 97 per cent in group 1, 91 per cent in group 2 and 95 per cent in group 3. Patients with bacteremias showed improvement in 93 per cent (group 1), 78 per cent (group 2) and 82 per cent (group 3) of cases. All failures were among patients with gram-negative bacteremias. Both antibiotic susceptibility of the bacteremic organism and granulocyte recovery correlated with patient improvement. Nephrotoxicity and ototoxicity were rare and were not significantly different in three groups of patients. Therefore, ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin appear to be equally efficacious and minimally toxic in this patient population. Excellent over-all results can be expected with these combinations provided the etiologic agent is susceptible.

Adolescent↗

PubMed1977

Treatment of pulmonary infections in patients with cystic fibrosis: a comparative study of ticarcillin and gentamicin.

The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated. Seventy-one percent of patients treated with ticarcillin alone responded favorably. The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone. Severity of the underlying disease was the most important determinant of response to treatment. Ticarcillin-resistant organisms were recovered during treatment in 50% of patients who received this drug; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clinical improvement. The ticarcillin-resistant strains persisted at follow-up, two to six months after completion of therapy, in only one of ten patients. No serious toxicity to ticarcillin was noted during the study period.

Adolescent↗

PubMed1976

Pharmacokinetics of ticarcillin in patients with abnormal renal function.

The pharmacokinetics of ticarcillin were determined in patients with abnormal renal function. In individuals with rates of creatinine clearance of greater than 60 ml per min, the half-life (+/- standard deviation) of ticarcillin was 71 +/- 6 min after intravenous administration. In patients with rates of creatinine clearance of 30-60 ml per min, 10-30 ml per min, and less than 10 ml per min, ticarcillin had a half-life of 3.0 +/- 0.6 hr, 8.5 +/- 2.1 hr, and 14.8 +/- 3.7 hr, respectively. Urinary concentrations of ticarcillin after intravenous administration were adequate at all levels of renal function. Ticarcillin was removed by hemodialysis with a reduction in half-life to 3.4 +/- 0.8 hr, but peritoneal dialysis was minimally effective in removing the drug. A program for the use of ticarcillin patients with renal insufficiency was outlined.

Clinical Trials as Topic↗

PubMed1979

Comparative study of anti-pseudomonas activity of azlocillin, mezlocillin, and ticarcillin.

The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal concentrations of the three drugs against 20 different strains of Pseudomonas aeruginosa and found significantly lower values for azlocillin than for the other two drugs. We then infused 5 g of each drug into 10 volunteers on three consecutive days and determined the serum levels of the three antibiotics at 1-h intervals from 1 to 6 h after injection. The levels of azlocillin were significantly higher than those of mezlocillin and ticarcillin (at 1 h: 236.55 mug/ml +/- 12.9 for azlocillin, 192.45 mug/ml +/- 28.8 for mezlocillin, and 131.5 mug/ml +/- 10.9 for ticarcillin). The inhibitory and bactericidal activities of the sera obtained 1 and 6 h after the injection against the same 20 strains of P. aeruginosa demonstrated a significantly greater anti-pseudomonas activity of azlocillin when compared with mezlocillin and ticarcillin; mezlocillin and ticarcillin had approximately the same activity. The mean values for bactericidal activity against the strains tested were 1/32 for azlocillin, 1/8 for mezlocillin, and 1/8 for ticarcillin. Azlocillin thus appears to be a promising anti-pseudomonas drug and should be tested in clinical trials.

Humans↗

PubMed1992

Efficacy of ticarcillin-clavulanic acid for treatment of experimental Staphylococcus aureus endocarditis in rats.

The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log10 CFU/g), or delayed until 24 h after infection, when the vegetations usually contained greater than 9 log10 CFU/g. Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses. Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by beta-lactamase-producing strains of S. aureus, illustrating the beta-lactamase-inhibitory activity of clavulanic acid in vivo. Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal beta-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active. These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections.

Animals↗

PubMed1976

Clinical and pharmacological studies of ticarcillin in gram-negative infections.

Twenty-seven patients with serious gram-negative infections were treated with ticarcillin in an average daily dosage of 237 mg/kg (range, 174 to 307 mg/kg). Ticarcillin was bactericidal for all infecting organisms in concentrations ranging from 31.2 to 125 mug/ml. Five of 8 patients (62%) with overwhelming Pseudomonas pneumonia were cured or improved, and 9 of 12 (75%) were cured of pneumonia caused by other gram-negative organisms. Of six extrapulmonary infections caused by Pseudomonas, five (83%) were cured or improved. In seven cases, the infecting organism reisolated during therapy was more resistant to ticarcillin than the primary isolate. The serum half-life of ticarcillin in three patients with renal failure was 11.2 +/- 1.0 h, and during hemodialysis it decreased to 6.3 +/- 1.8 h. There were two episodes of superinfection with resistant organisms. Thirteen patients (48%) manifested eosinophilia, one of whom had severe urticaria. Prolongation of bleeding time was attributable to ticarcillin in two patients. Ticarcillin appears to be effective for therapy of serious gram-negative infections in dosages 30 to 50% less than those recommended for carbenicillin.

Adult↗

PubMed1975

In vitro activity of ticarcillin, carbenicillin and ampicillin against some gram-negative bacilli.

alpha-Carboxy-3-thienylmethyl penicillin (ticarcillin) is a relatively new semisynthetic penicillin which is more active than carbenillin against Pseudomonas aeruginosa. Among the strains tested, those isolated from the respiratory tract showed an increased susceptibility to carbenicillin and ticarcillin. As with carbenicillin, synergistic activity against P. aeruginosa could be demonstrated with ticarcillin in combination with gentamicin. Like other penicillins, the antibacterial activity was influenced by the inoculum size. The antibacterial activity of ticarcillin showed the compound to be almost equally active with carbenicillin and ampicillin against Escherichia coli and Klebsiella aerogenes, but less active than acrbenicillin and ampicillin against indole-negative Proteus strains. Regarding the indole-positive Proteus species, at relatively low antibiotic concentrations the proportion of strains sensitive to ticarcillin was greater than to carbenicillin or ampicillin whereas at relatively high antibiotic concentrations the converse was the case. It is interesting to note that a high proportion of strains of E. coli and K. aerogenes were resistant to the three penicillins even at a concentration of 200 mug/ml, while 70% of Proteus strains were inhibited by these drugs at the same concentration. Disc susceptibility tests with ticarcillin were carried out according to BAUER-KIRBY method.

Ampicillin↗