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At least 19 recordsLinked to original sources
PubMed1990

Ocular and serum disposition kinetics of cloxacillin after topical administration of benzathine cloxacillin and intravenous administration of sodium cloxacillin to calves.

Disposition kinetics of cloxacillin were examined in calves after topical administration of benzathine cloxacillin and single IV administration of sodium cloxacillin, and the susceptibility of 17 field isolates of Moraxella bovis was measured. For the IV pharmacokinetic phase, sodium cloxacillin was administered at dosage of 10 mg/kg of body weight to male Holstein calves (n = 6, weighing 146 to 170 kg), and serum concentration of cloxacillin was measured thereafter for 10 hours. For the ocular pharmacokinetic phase, 6 calves were given either of 4 benzathine cloxacillin topical formulations consisting of 50-, 125-, 250-, or 375-mg doses. Treatment was repeated every 10 days until all 4 benzathine cloxacillin dosages were tested in the same 6 calves. Blood and tears were collected for 72 hours after each benzathine cloxacillin formulation was administered, and the concentration of cloxacillin in each specimen was measured, using a bioassay. The minimal inhibitory concentration of cloxacillin for 17 field isolates of M bovis was determined by use of an agar pour-plate dilution assay. After single IV administration of sodium cloxacillin, its half-life, body clearance, and volume of distribution were 19.5 +/- 12.8 minutes, 18.3 +/- 2.2 ml/min.kg, and 496 +/- 290 ml/kg, respectively. After topical administration of benzathine cloxacillin, cloxacillin concentration in lacrimal fluid peaked between 30 and 45 minutes and ranged between 963 micrograms/ml and 3,256 micrograms/ml for the 125- and 375-mg doses, respectively. There was no detectable cloxacillin activity in the lacrimal fluid of any calf by 36 hours after topical administration of benzathine cloxacillin, and cloxacillin was not detected in the serum at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1991

[Teicoplanin versus cloxacillin, cloxacillin-gentamycin and vancomycin in the treatment of experimental endocarditis caused by methicillin-sensitive Staphylococcus aureus].

Thirty-three rabbits, (12 in the control group and 21 treated, 5 with teicoplanin, vancomycin and cloxacillin-gentamycin and 6 with cloxacillin alone) with methicillin-sensitive Staphylococcus aureus (MSSA) experimentally induced endocarditis were studied to evaluate the efficacy of teicoplanin and its comparison with cloxacillin, vancomycin and cloxacillin-gentamycin. The rabbits were treated during three days. Mortality, blood cultures at 48 and 72 hours and the number of colonies forming units per gram of vegetation were then evaluated. There was statistically significantly differences between the control group and the 4 treated groups in respect of mortality (p less than 0.001), and blood culture's negativity at 48 and 72 hours (p less than 0.001), but not among the various groups of treatments. The CFU number of the vegetations were also significantly different between control and treatment groups (p less than 0.001). Cloxacillin and the combination cloxacillin-gentamycin lowered the CFU number more than teicoplanin and vancomycin (p less than 0.005). These results, allowed us to conclude than teicoplanin may be used as an alternative of standard treatments in infective endocarditis due to MSSA.

Animals↗
PubMed1991

[Efficacy evaluation of cloxacillin and cloxacillin-gentamicin in an experimental model of methicillin-sensitive Staphylococcus aureus].

23 rabbits with Staphylococcus aureus methicillin-sensitive, SAMS, experimentally induced endocarditis (EIE) were studied to compare the efficacy of cloxacillin vs the association cloxacillin-gentamicin. Twelve animals made the control group and 11 the treated ones, 5 with cloxacillin-gentamicin and 6 with cloxacillin. The animals were treated 3 days, then, mortality, blood cultures at 48 and 72 hours and the title of the unit-forming colonies per gram of vegetation (UFC/g) were evaluated. The control group had a mortality of 100% in the first 72 hours, its blood cultures were positive at 48 and 72 hours and the UFC/g was 10,48 o 0.20. There was statistical significance between the control group and both treatment, in mortality, blood culture's positivity and the UFC/g of vegetation. This results confirm the similar efficacy of cloxacillin either alone or in combination in the treatment of SAMSIE and the effectiveness of the experimental model to evaluate antimicrobial treatments.

Animals↗
PubMed1990

Effect of cloxacillin prophylaxis on the bacterial flora of craniotomy wounds.

During a double-blind placebo-controlled study, the effect of cloxacillin prophylaxis in craniotomies on samples taken for culture from 334 operation wounds in 279 patients was assessed. Patients and operations were equally divided over the cloxacillin and placebo groups. In the cloxacillin group significantly fewer samples contained microorganisms than was the case in the placebo group both just after the incision was made (p less than 0.05) and just before closure of the wound (p less than 0.001). The contaminating bacteria found most frequently were Propionibacterium acnes and Staphylococcus epidermidis. For material collected immediately after the incision, the percentage of cultures positive for S. epidermidis was significantly (p = 0.001) lower in the cloxacillin group than in the placebo group; the percentage of cultures with P. acnes did not differ between the two groups. For samples taken just before the wound was closed, the percentage of cultures with P. acnes or S. epidermidis was significantly (p = 0.008 and 0.003, respectively) lower in the cloxacillin than in the placebo group. In the placebo group neurosurgical infections occurred with P. acnes and/or S. epidermidis as causative microorganisms; in almost all cases those bacteria could be cultured from the edge of the wound. In none of the patients with an infection caused by S. aureus was the bacteria found in the operation area. In 2/6 infections in the cloxacillin group the infecting microorganisms could be cultured from the operation area. These findings support a significant reduction in the infection rate after craniotomy under cloxacillin prophylaxis compared with placebo.

Cloxacillin↗
PubMed1975

Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis.

1 A pharmacokinetic study on flucloxacillin and cloxacillin was performed to investigate the factors contributing to the higher serum concentrations reported for the former after oral administration. 2 The results obtained in a study performed in a group of volunteers with flucloxacillin administered orally and by continuous infusion, were compared with the results of a similar investigation with cloxacillin. Patients on chronic intermittent haemodialysis received flucloxacillin orally and as a single i.v. injection. The results of this part of the study were compared with those of an earlier study on cloxacillin in haemodialysis patients. Serum and urine concentrations of flucloxacillin and cloxacillin were determined by bio-assay, and a one-compartment model was used for the calculations. 3 Higher serum concentrations reached after oral administration of flucloxacillin as compared with cloxacillin were based not only on better oral absorption (53.7% and 32.9%, respectively) but also on slower (renal and extra-renal) elimination (T1/2 : 46 and 32 min, respectively). A significant difference between the apparent volumes of distribution of flucloxacillin and cloxacillin, which could contribute to higher serum concentrations, could not be demonstrated. Considerable individual variation occurs in the rate and amount of oral absorption, especially in patients. The elimination rate of flucloxacillin in haemodialysis patients (T1/2 : 2h 53 min) corresponds with the extra-renal elimination rate in healthy subjects. No influence of haemodialysis on the elimination rate constant of flucloxacillin was found; total plasma clearance was, however, slightly but significantly higher during dialysis.

Administration, Oral↗
PubMed1991

Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers.

Pharmacokinetic and pharmacodynamic interactions between Org 10172 (intravenous bolus injection of 3,250 anti-Xa units), which is a low-molecular-weight heparinoid, cloxacillin (500 mg orally four times daily for 3 days), and ticarcillin (4,000 mg intravenously four times daily for 2 days) were evaluated in two separate studies with healthy male volunteers (n = 18). Both cloxacillin and ticarcillin caused a significant increase in elimination half-life of anti-Xa activity, i.e., from 31 +/- 10 to 54 +/- 23 h and from 27 +/- 6 to 42 +/- 13 h, respectively (P less than 0.05). Ticarcillin decreased clearance (11%) and increased apparent volume of distribution (35%) (P less than 0.05), while for cloxacillin, these differences did not reach statistical significance. These changes in disposition of Org 10172 by the penicillins were not accompanied by important pharmacodynamic changes as evaluated by coagulation tests, platelet aggregation, and bleeding time. Cloxacillin appeared to influence blood coagulation (prolongation of the activated partial thromboplastin time and shortening of thrombin time; P less than 0.05) and facilitated thrombin-induced platelet aggregation, which coincided with a shorter bleeding time during the combined treatment in comparison with the time during treatment with Org 10172 alone (P less than 0.05). In conclusion, the disposition of Org 10172 was slightly changed by cloxacillin and ticarcillin, and, unexpectedly, cloxacillin appeared to have mild procoagulant effects.

Adolescent↗
PubMed1990

Topically applied benzathine cloxacillin for treatment of experimentally induced infectious bovine keratoconjunctivitis.

The efficacy of an ophthalmic ointment containing benzathine cloxacillin for treatment of infectious bovine keratoconjunctivitis was determined in 2 experiments. In the first experiment, Holstein calves (n = 6/group) were inoculated with Moraxella bovis and treated on postinoculation days 3 and 6 with either topically applied benzathine cloxacillin (250 mg/eye) or long-acting oxytetracycline formulation (20 mg/kg of body weight, IM). A third group of inoculated calves remained untreated as controls. For the second experiment, 4 groups of calves (n = 6/group) were inoculated and treated on postinoculation days 3 and 6 with 50, 125, 250, or 375 mg of benzathine cloxacillin; a fifth untreated group served as controls. Ocular specimens were obtained for microbiologic culture, and eyes were observed and assigned a clinical score daily. Eyes were photographed on alternate days. Ulcer surface area was measured, using a planimeter. In experiment 1, the week-2 ulcer surface area measurements for both groups of treated calves were smaller than those for controls. There was a greater frequency of M bovis isolation from the ocular secretions of controls than from those of benzathine cloxacillin-treated calves during postinoculation weeks 2 and 3. The number of M bovis isolations from the benzathine cloxacillin- and oxytetracycline-treated calves was not significantly different at any sample collection interval. On week 3, the scores of the benzathine cloxacillin-treated calves were smaller than those of controls. In experiment 2, calves of the 250- and 375-mg groups had smaller ulcer surface area measurements than did controls on week 2. By week 3, calves of the 375-mg group had smaller scores than did controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMedDate not supplied

Clindamycin and cloxacillin compared in the treatment of skin and soft-tissue infections.

The subjects were 61 patients with skin or soft-tissue infections treated at the Cipto Mangunkusumo General Hospital in Jakarta, Indonesia. The patients, aged 15 to 59 years (40 females, 21 males), were randomly assigned to receive 300 mg of clindamycin or 500 mg of cloxacillin orally thrice daily for seven days. On day 8, the infections were cured in seven of the 31 clindamycin-treated patients and in three of the 30 cloxacillin-treated patients; on day 15, 27 of the clindamycin group and 18 of the cloxacillin group were cured; four clindamycin-treated patients and 11 cloxacillin-treated patients were improved; and one cloxacillin-treated patient failed. The between-group differences were not statistically significant. Pretreatment positive cultures were obtained in 40 patients, including Staphylococcus aureus in 24, group A beta-hemolytic streptococci in five, and a combination of S aureus and beta-hemolytic streptococci in four. Side effects were reported by three clindamycin-treated patients (gastric upset, nausea, and headache) and one cloxacillin-treated patient (nausea). Abnormal changes in laboratory test results from before to after treatment were noted in both patient groups and were probably not attributable to either drug. It is concluded that clindamycin is a safe and effective agent in the treatment of skin and soft-tissue infections.

Adolescent↗
PubMed1977

Microbiological relevance and clinical potential of ampicillin-cloxacillin synergism.

Recent demonstration "in vitro" that combinations of ampicillin and cloxacillin, using concentrations at which neither were previously effective, will kill certain resistant Gram negative bacteria, has important clinical potential. We therefore studied 50 ampicillin resistant Gram negative rods cultured from septicemic patients for synergism. 7 of 23 E. coli strains with a minimal bactericidal concentration (MBC) of 128 microgram/ml were killed by combinations containing 4-32 microgram/ml ampicillin and 16-32 microgram/ml cloxacillin. These same strains were also resistant to cephalothin. Synergism was also noted in 1/4 strains of Enterobacter, 1/3 strains of Serratia, 5/14 strains of Klebsiella and 1/6 strains of Pseudomonas. In separate experiments ampicillin (56 mg/kg) and cloxacillin (14 mg/kg) was administered intravenously over a period of thirty minutes. Peak serum levels measured simultaneously at the end of the infusion were 235 +/- 11 (SEM) microgram/ml for ampicillin and 85 +/- 7 microgram/ml for cloxacillin. Levels of ampicillin/cloxacillin measured one and two hours after the infusion were 117/32 and 43/8 microgram/ml. T 1/2 of ampicillin and cloxacillin were 0.8 and 0.5 h respectively. Since the serum concentrations of both antibiotics measured one hour after the infusion were greater that levels required for "in vitro" synergism, we suggest that combinations of ampicillin and cloxacillin would be of importance in the treatment of Gram negative septicemia, since such therapy would increase the bactericidal effect of the sera without increasing the risk of toxic side effects.

Ampicillin↗
PubMed1976

Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects.

Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).

Administration, Oral↗
PubMed1992

Role of tolerance in cloxacillin prophylaxis of experimental Staphylococcus aureus endocarditis.

The role of tolerance was investigated in the prophylaxis of Staphylococcus aureus endocarditis with cloxacillin in rats. The effect of a single dose of 500 mg/kg, two 80 mg/kg doses 3 h apart, and a single dose of 80 mg/kg, alone or in combination with a single dose of 4 mg of gentamicin/kg, were compared for a tolerant strain of S. aureus and its isogenic nontolerant variant. At all dosages, cloxacillin was significantly less effective in preventing endocarditis with the tolerant strain than with the nontolerant variant. With the high dose of cloxacillin or two successive lower doses, nearly complete protection could be obtained against the nontolerant strain. However, for the tolerant strain, only the combination of cloxacillin and gentamicin afforded almost complete protection. For the tolerant strain, no serum bactericidal activity was found at the time of bacterial challenge after an injection of any dose of cloxacillin. These results suggest that the in vitro phenomenon of tolerance may have relevance in vivo.

Animals↗
PubMed1978

Cloxacillin distribution in the rabbit eye after intravenous injection.

Distribution of isotopically labelled and intravenously injected cloxacillin was studied in rabbit eye. The antibiotic concentration determined by liquid scintillation counting proved to be a reliable measure of the total antibiotic concentration when controlled by microbiological assay. In the rabbit eye after an intravenous injection of 50 mg/kg of cloxacillin sodium, longlasting antibiotic concentration regarded as therapeutic against penicillinase producing staphylococci was obtained in all vascularized ocular structures and in the cornea. The antibiotic present in the iris and ciliary body, and in the retina and choroid preparations, proved to be partly intravascular, whereas it penetrated better into the extravascular tissue compartment of the sclera and limbal area. Cloxacillin failed to achieve a therapeutic antibiotic concentration in the vitreous body and in the lens. Administration of probenecid had an enhancing effect on ocular cloxacillin concentration allowing improved drug diffusion into the eye by means of an elevated plasma concentration. No specific ocular effect of probenecid was noticed. Therapeutic concentration of cloxacillin in the aqueous humour, otherwise barely achieved, was more satisfactorily obtained with a previous injection of probenecid.

Animals↗
PubMed1978

Effect of paracentesis on ocular cloxacillin concentration.

The effect of anterior chamber puncture on cloxacillin concentration in the rabbit eye after intravenous injection was studied using a radioactive tracer method. The enhancement in drug concentration caused by paracentesis was most immediate and significant in the iris-ciliary body preparation. It was soon followed by high cloxacillin concentration in the aqueous humour, which contributed to elevated cloxacillin levels in the cornea, lens and anterior vitreous body, when compared to normal material. Contrary to normal eyes, cloxacillin concentration in the cornea of the punctured eyes was higher than in the limbal area. The morphological changes occurring after paracentesis are discussed. The breakdown of the hydrodynamic equilibrium in the eye, suggested as the only change after paracentesis by Raviola (1974), cannot merely explain the cloxacillin concentration changes measured in the punctured eye.

Animals↗
PubMed1990

Pharmacokinetic analysis of cloxacillin loss in children undergoing major surgery with massive bleeding.

To determine the magnitude of cloxacillin loss during surgical procedures involving significant blood loss and high fluid replacement, we compared the pharmacokinetics of cloxacillin in children during craniomaxillofacial surgery with the disposition of the drug in healthy young adult volunteers with intact circulation. Blood loss during craniofacial operations may exceed blood volume, in some cases by as much as three times. Hemodynamic replacement with electrolyte solutions and blood products, which do not contain the drug, further dilute cloxacillin concentrations. In the patients that we studied, mean drug loss was estimated at 71%. Cloxacillin concentrations in serum fell below the lower range of the MIC for Staphylococcus aureus during significant portions of the surgical procedures. Thus, the traditional dosing of cloxacillin during prolonged operations with massive blood loss is inadequate. A more frequent dosing interval or priming of all replacement fluids with the drug may be required to maintain therapeutic levels. Our findings suggest that massive blood loss is likely to have a dramatic effect on the level of any drug with a small distribution volume. If such a drug is essential to the patient's well-being (e.g., antibiotics, antiarrhythmics, and anticonvulsants), it must be replaced promptly.

Adolescent↗
PubMed1992

Cloxacillin-induced acute tubulo interstitial nephritis.

OBJECTIVE: To report a case of possible cloxacillin-induced acute tubulo interstitial nephritis (AIN). CASE SUMMARY: A 15-year-old male patient presented with hypertension, edema, lumbar pain, sterile pyuria, eosinophiluria (ten percent), and severe renal dysfunction three months after the ingestion of cloxacillin. A renal biopsy revealed diffuse edema and inflammatory infiltrate of the interstitium (five percent eosinophils). He received four sessions of peritoneal dialysis with dramatic improvement in urinary output and renal function. His biochemical parameters returned to normal values 21 days after admission, without the use of glucocorticosteroids. DISCUSSION: Published case reports on AIN induced by penicillin and related drugs are reviewed and compared. The role of interstitial edema in acute renal failure associated with drug-induced AIN is mentioned. CONCLUSIONS: AIN is a rare but significant complication of therapy with penicillin and related drugs. The clinical picture is similar for all of these drugs, but skin rash and fever are absent in AIN induced by cloxacillin and cloxacillin-related drugs. Dialysis improved the patient's urinary output and renal function. Beta-lactam antibiotics should be avoided in patients with cloxacillin-induced AIN.

Adolescent↗
PubMed1991

Evaluation of cloxacillin concentrations in plasma and muscle tissue during cardiopulmonary bypass.

Concentrations of cloxacillin in plasma and deep thoracic muscle tissue were measured in 10 patients who underwent elective coronary bypass surgery or valve replacement. One g of cloxacillin was administered after the induction of anaesthesia and 1 g cloxacillin was added to the oxygenator pump priming fluid before the start of the procedure. Blood and tissue samples were obtained before, during and after cardiopulmonary bypass. The relation between unbound plasma concentrations and total tissue contents of the drug was calculated. It was shown that measurement of the free plasma concentration may provide fairly reliable information on the free concentrations of cloxacillin in the tissues, and that determination of tissue contents may therefore not be necessary. Due to the administration of the second dose of cloxacillin at the start of cardiopulmonary bypass free tissue contents were just adequate in most patients. However, to obtain adequate tissue concentrations after bypass it is recommended that a third dose of the antibiotic be administered before the end of the operation.

Adult↗
PubMed1978

Resistance of staphylococci to penicillin-G and cloxacillin.

Staphylococcus aureus and epidermidis species from patient cultures and hospital environmental samples were studied for resistance to Penicillin-G and Cloxacillin, a penicillinase resistant penicillin. Only 4--7% of the 232 Staphylococcus aureus strains were sensitive to Penicillin-G; 40--41% were sensitive to Cloxacillin. Patient strains (57) of Staphylococcus epidermidis were sensitive to Penicillin-G in 29% and to Cloxacillin in 53% of the cases. The incidence of sensitivity of the hospital strains (50) of Staphylococcus epidermidis to Penicillin-G was 78% and to Cloxacillin was 93%. In view of their high resistance to Cloxacillin, the strains were evaluated for sensitivity to Gentamicin, an alternate choice for antibiotic therapy. Approximately 90% of the Staphylococcus aureus strains were sensitive to Gentamicin while 99% of the Staphylococcus epidermidis strains were sensitive. This study indicates that differences may exist in regard to antibiotic resistance patterns in various localities and this should be evaluated.

Cloxacillin↗
PubMed1991

Role of tolerance in cloxacillin treatment of experimental Staphylococcus aureus endocarditis.

The role of Staphylococcus aureus tolerance was investigated in endocarditis in rats. The efficacies of cloxacillin, gentamicin, and a combination of the two were compared for animals infected with a tolerant strain, its kill-sensitive variant, or a nonisogenic nontolerant strain of S. aureus. Cloxacillin was significantly less effective for treating the tolerant than for the nontolerant strains. The addition of gentamicin to cloxacillin reduced bacterial numbers in endocardial vegetations for the tolerant strain comparable to the reduction by cloxacillin alone for the nontolerant strains, but had no additional effect for the nontolerant strains. Isolates from animals infected with the tolerant or nontolerant strains during antibiotic treatment remained tolerant or nontolerant. These results show that the in vitro phenomenon of tolerance is relevant in vivo.

Animals↗