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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↗
PubMed1997

No effect of diclofenac on the pharmacokinetics of cloxacillin.

We studied the influence of diclofenac on the pharmacokinetics of cloxacillin in healthy volunteers, 60 years or older, as well as the possible effect of cloxacillin and diclofenac on urinary protein excretion. In a randomized, double-blind, cross-over study 15 subjects were given 1 g cloxacillin, and placebo or 75 mg diclofenac, as single intravenous doses. Plasma concentrations of cloxacillin were followed over 10.5 hr, and urine excretion of cloxacillin over 24 hr. The effect of the drugs on urinary excretion of protein indicators of glomerular (albumin, IgG) and tubular (protein HC) function was also studied. Total plasma clearance of cloxacillin was with placebo 219 +/- 51 (mean +/- S.D.), and with diclofenac 212 +/- 39 ml/min./1.73 m2 (ns); renal clearance was 97 +/- 21 and 96 +/- 24 ml/min./1.73 m2, respectively (ns). The terminal t1/2 of cloxacillin was 1.03 +/- 0.42 hr with placebo, and 1.12 +/- 0.37 with diclofenac (ns). The mean ratio of AUC0-infinity's (cloxacillin plus diclofenac/cloxacillin plus placebo) was 1.03 (90% CI: 0.99, 1.08). Urinary excretion of the proteins was low and was not increased by cloxacillin or diclofenac. In healthy volunteers, 60 years or older, diclofenac does not alter cloxacillin pharmacokinetics, and neither cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.

Aged↗
PubMed1968

Synergistic antibacterial activity of ampicillin-cloxacillin mixtures against Proteus morganii.

Synergistic antibacterial effects of mixtures of ampicillin and cloxacillin and induced penicillinases were investigated in 48 strains of Proteus. The serial tube dilution method was used to determine the minimal inhibitory concentration of ampicillin, cloxacillin, and 2:1 and 1:1 mixtures of ampicillin and cloxacillin. Production of penicillinases was determined by the cellulose acetate membrane method, with ampicillin, cloxacillin, mixtures of ampicillin and cloxacillin, penicillin G, and cephalothin as inducing agents and as substrates for penicillinase. Synergism occurred against P. morganii, but against no other species. The 1:1 ampicillin-cloxacillin combination was synergistic against 13 of 17 P. morganii strains; the 2:1 combination was synergistic against only 9 strains. Penicillinases, demonstrated in all species except P. mirabilis, hydrolyzed penicillin G and cephalothin. Although only P. vulgaris hydrolyzed ampicillin, no species of Proteus hydrolyzed cloxacillin or the ampicillin-cloxacillin mixtures. Penicillinases were, however, induced by ampicillin, cloxacillin, and the mixtures. There was no relationship between production of penicillinase and synergism with mixtures of ampicillin and cloxacillin.

Ampicillin↗
PubMedDate not supplied

Allergy to cloxacillin with normal tolerance to amoxicillin and cefuroxime.

BACKGROUND: Cloxacillin is a semisynthetic penicillin widely used in nonmethicillin resistant Staphylococcus aureus infections. Several hypersensitivity reactions to cloxacillin have been reported, although IgE-mediated allergic reactions to the drug are rare and there is little information about possible tolerance to other semisynthetic penicillins or cephalosporins in patients with cloxacillin allergy. We present 2 patients with demonstrated IgE-mediated allergy to cloxacillin and tolerance to amoxicillin and cefuroxime. CASE REPORTS: Case 1. A 47-year-old woman began treatment with cloxacillin due to acute cellulitis. After ingesting 500 mg of the drug, she experience generalized maculopapular eruption and facial angioedema. Case 2. A 55-year-old woman presented an episode of acute urticaria and labial angioedema 60 minutes after ingesting 500 mg of cloxacillin for a skin abscess. METHODS AND RESULTS: Skin prick tests were positive to cloxacillin in case 1 and negative in case 2. However, an intradermal test was positive to cloxacillin (2 mg/ml) in case 2. Simple-blind oral challenge tests with amoxicillin (1 g) and cefuroxime (500 mg) were well-tolerated by both patients. CONCLUSIONS: We present 2 patients allergic to cloxacillin with normal tolerance to other betalactam antibiotics, confirming that cross-reactivity among these antibiotics seems to be uncommon. Complete allergy study, including an oral challenge test, should be considered in these patients.

Abscess↗
PubMed1984

Staphylococcal endocarditis in rabbits treated with a low dose of cloxacillin.

Rabbits with established staphylococcal endocarditis, injected twice at an interval of 2 h with either 0.5 mg of cloxacillin per kg or saline, were sacrificed 2.5 h after the second injection. Vegetations were excised, weighed, and cultured, and ultrathin sections were prepared and examined by light microscopy, transmission electron microscopy, and scanning electron microscopy. Several affected valves were examined histologically. Concentrations of cloxacillin in serum were determined 1 and 3 h after dosage. Staphylococci grown on membranes placed on agar containing 0.09 micrograms of cloxacillin per ml and in broth at the same cloxacillin concentration (one-third of the MIC) were examined by transmission electron microscopy. The mean numbers of CFU per gram of vegetations from control and treated rabbits were 2.28 X 10(10) and 1.31 X 10(10), respectively. Vegetations of treated rabbits contained staphylococci of normal size and form as well as organisms two to six times larger than normal with multiple cross walls. Larger bacterial cells were usually located in areas close to blood; cells of normal size were usually embedded in fibrin. The structures of these staphylococci and those grown on membranes in the presence of 0.09 micrograms of cloxacillin per ml were comparable but were different from those grown in broth containing this concentration of cloxacillin. Concentrations of cloxacillin in serum were 0.166 micrograms/ml at 1 h and 0.286 micrograms/ml at 3 h after dosage. The similarities in ultrastructure between staphylococci in vegetations of treated rabbits and staphylococci grown on membranes suggest that the vegetations contained approximately 0.09 micrograms of cloxacillin per g. Thus, antibiotic penetration from blood into vegetations and diffusion into fibrin were limited.

Animals↗
PubMed2006

Assessment of antimicrobial transfer from treated to untreated mammary gland quarters by use of high-pressure liquid chromatography for detection of cloxacillin in milk samples from nonlactating dairy cows.

OBJECTIVE: To determine whether half-udder intramammary infusion of cloxacillin results in transfer of cloxacillin from treated to untreated mammary gland quarters within nonlactating cows, and, if so, at what concentrations, and to determine whether selection of ipsilateral versus diagonal-contralateral quarters for treatment affects cloxacillin transfer among quarters. ANIMALS: 20 Holstein-Friesian cows from a dairy herd. PROCEDURES: A within-cow half-udder comparison trial was used in which 2 of 4 mammary gland quarters (ipsilaterally or diagonally) received an intramammary infusion of cloxacillin on day 1 of the nonlactating period. Three days later, milk samples were taken from all untreated quarters and high-pressure liquid chromatography was used to detect and quantify milk cloxacillin concentrations. RESULTS: Cloxacillin was detected in 25% of all untreated mammary gland quarters. Mean cloxacillin concentration in untreated quarters was below minimum inhibitory concentrations for targeted mastitis pathogens. No significant difference in cloxacillin concentrations was found in the ipsilateral or diagonal treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Within-cow half-udder comparison trials are valid for antimicrobial trials in nonlactating cows, although transfer of antimicrobials does occur in trace concentrations. Ipsilateral or diagonal-contralateral treatment designs perform similarly. This type of design is economical for researchers, although care must be taken to account for within-cow clustering of mammary gland quarter data.

Animals↗
PubMed1996

Effectiveness of cloxacillin with and without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis. A randomized, controlled trial.

BACKGROUND: It is often difficult to administer extended antibiotic therapy in the hospital for right-sided Staphylococcus aureus endocarditis. Although the effectiveness of single-drug therapy given for 4 to 6 weeks and that of two-drug therapy given for 2 weeks have been shown, no data are available on the effectiveness of short-course single-drug therapy. OBJECTIVE: To compare the efficacy of cloxacillin alone with that of cloxacillin plus gentamicin for the 2-week treatment of right-sided S. aureus endocarditis in intravenous drug users. DESIGN: Open, randomized study. SETTING: An academic tertiary care hospital in Barcelona, Spain. PATIENTS: 90 consecutive intravenous drug users who had isolated tricuspid valve endocarditis caused by methicillin-susceptible S. aureus, had no allergy to study medications, and had no systemic infectious complications that required prolonged therapy. An efficacy subset consisted of 74 of these patients who did not meet an exclusion criterion. INTERVENTION: Cloxacillin (2 g intravenously every 4 hours for 14 days) alone or combined with gentamicin (1 mg/kg of body weight intravenously every 8 hours for 7 days). MEASUREMENTS: Clinical or microbiological evidence of active infection after 2 weeks of therapy, relapse of staphylococcal infection, or death. RESULTS: In an analysis of the efficacy subset, treatment was successful in 34 of the 38 patients who received cloxacillin alone (89% [95% CI, 75% to 97%]) and 31 of the 36 patients who received cloxacillin plus gentamicin (86% [CI, 71% to 95%]). Three patients died: one in the cloxacillin group and two in the combination therapy group. Of the 37 patients who completed 2-week treatment with cloxacillin, 34 (92%) were cured, and 3 (8%) needed prolonged treatment to cure the infection. Of the 34 patients who completed 2-week treatment with cloxacillin plus gentamicin, 32 (94%) were cured and 2 (6%) required treatment for 4 weeks. One patient in the combination group had relapse. CONCLUSIONS: A penicillinase-resistant penicillin used as single-agent therapy for 2 weeks was effective for most patients with isolated tricuspid endocarditis caused by methicillin-susceptible S. aureus. Adding gentamicin did not appear to provide any therapeutic advantages. Additional studies to confirm the therapeutic equivalence of short-course therapy with penicillinase-resistant penicillin alone and therapy with combined regimens are warranted.

Anti-Bacterial Agents↗
PubMed1986

[Cloxacillin concentration in suction fluid following flash antibiotic therapy during insertion of a hip prosthesis].

Since 1982 we have administered cloxacillin intraoperatively during total hip replacement. 1 g cloxacillin is injected intravenously at induction of anesthesia, followed by 1g every hour until the end of the procedure or a total of 6 g. In our study, cloxacillin concentrations were determined in the fluid collected from the deep suction catheter inserted at the end of the surgical procedure. Fluid samples were collected 2 h, 4 h, 6 h, 8 h and 24 hours after the last injection of cloxacillin. Serum samples were taken 2 h, 6 h and 24 hours after the last injection. Cloxacillin was assayed using an agar-diffusion microbiologic method. 18 patients were studied. Each had received 3 to 5 g cloxacillin over 3 to 5 hours. Mean suction catheter fluid concentrations were to 69.7 micrograms/ml, 37.6 micrograms/ml, 24.2 micrograms/ml, 15.5 micrograms/ml, and 6.8 micrograms/ml respectively in the samples collected 2 h, 4 h, 6 h, 8 h and 24 hours after the last injection of cloxacillin. Mean serum concentrations were 34.1 micrograms/ml, 4.2 micrograms/ml, and 0 microgram/ml respectively 2 h, 6 h and 24 hours after the last injection. Our results indicate that cloxacillin concentrations within the hip joint are probably effective against staphylococci for 8 to 12 hours.

Aged↗
PubMed1983

Penicillin (cloxacillin)-tolerant Staphylococcus aureus from bovine mastitis: identification and lack of correlation between tolerance in vitro and response to therapy in vivo.

Twenty-four isolates of Staphylococcus aureus from naturally occurring cases of bovine mastitis were examined in vitro for resistance to cloxacillin. All strains produced penicillinase and none showed intrinsic resistance (methicillin resistance) to cloxacillin. The minimum inhibitory concentration of cloxacillin for all these strains was normal (low) but differences were found between them in their sensitivities to the bactericidal action. Three were considered to be tolerant to cloxacillin and a further five possibly so. In a mouse model of mastitis there was no difference in the response to intramammary therapy with cloxacillin between cloxacillin-sensitive or tolerant strains of S aureus and a known methicillin-resistant strain was similarly sensitive to cloxacillin therapy in vivo. It is concluded that cloxacillin tolerance may have little clinical significance in mastitis therapy.

Acute Disease↗
PubMed1999

Comparison of ex-vivo serum bactericidal activity of cefepime, ceftazidime and cloxacillin against Staphylococcus aureus.

Cefepime (1 g), ceftazidime (1 g), and cloxacillin (2 g) were administered intravenously to 10 volunteers each. After infusion of a single dose over 30 min, blood samples were obtained at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h (for ceftazidime at 0.5 and 4 h) after dosing. Drug levels were determined by the bioassay method. Serum bactericidal activity against five clinical isolates of cloxacillin-susceptible Staphylococcus aureus were determined by the microdilution method according to the National Committee for Clinical Laboratory Standards guidelines. The mean peak serum level was 76.88 +/- 24.71 mg/L for cefepime, 42.8 +/- 15.98 mL/L for ceftazidime, and 92.81 +/- 24.7 mg/L for cloxacillin. Concentrations of cefepime were detected during the whole testing period (mean trough level, 1.43 +/- 0.9 mg/L at 12 h), whereas concentrations of cloxacillin were measurable up to 5 h after administration (mean trough level, 0.90 +/- 0.97 mg/L). The mean peak reciprocal bactericidal titers were 29.41 for cefepime, 5.6 for ceftazidime, and 377 for cloxacillin. Effective bactericidal titers were detected as long as 5 h for cefepime (approximately 40% of the dosing interval) and 3 h for cloxacillin (at least 50% of the dosing interval). For ceftazidime, serum bactericidal activity was markedly lower compared with that of cefepime. Although cefepime has demonstrated an improved antistaphylococcal bactericidal activity compared with ceftazidime, it was somewhat lower than that of cloxacillin.

Adult↗
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↗
PubMed2006

Comparative activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus experimental endocarditis.

OBJECTIVES: To compare the activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus and to determine how rapidly their bactericidal activity occurs in cardiac vegetations. METHODS: In vitro and in vivo studies using an experimental model of endocarditis in rabbits. Animals were treated for 1, 2 or 3 days with cloxacillin 200 mg/kg intramuscularly three times a day or vancomycin 25 mg/kg intravenously twice a day. RESULTS: Cloxacillin and vancomycin at concentrations 4- and 16-fold the MIC produced a modest decrease in the number of microorganisms at 4 h. After 24 h, cloxacillin produced a decrease in the counts of staphylococci from 2.19 to 4.84 log10 cfu/mL of inoculum. Only concentrations of vancomycin from 16- to 32-fold the MIC resulted in equivalent decreases. After 24 h of treatment, both antibiotics were equally effective in preventing mortality of rabbits. Cloxacillin produced a greater decrease in the number of staphylococci than vancomycin (3.50+/-2.18 log10 cfu/g vegetation and 6.25+/-1.28 log10 cfu/g vegetation, respectively; P<0.05) and 41% of rabbits had sterile vegetations in comparison with none with vancomycin (P=0.035). After 48 and 72 h of treatment, both antimicrobials exhibited equivalent activity. CONCLUSIONS: Vancomycin was less rapidly bactericidal than cloxacillin in vivo.

Animals↗
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↗
PubMed1988

Simultaneous high-pressure liquid chromatographic analysis of ampicillin and cloxacillin in serum and urine.

A rapid, specific and sensitive high pressure liquid chromatographic (HPLC) assay for the simultaneous determination of ampicillin and cloxacillin in serum and urine is developed. Ampicillin, cloxacillin and cephalexin (internal standard) were eluted from a 6.5 mu Synchropack RPP reversed phase column at ambient temperature using a mobile phase comprised of methanol:water (3/7v/v) and containing 0.011 M sodium-n-octane sulphonate, 0.005 M NaH2PO4 and 1.3% v/v of 0.5 M HCl (pH 2.7). The analysis time required no longer than 11 min. Equations are presented for the linear relationships between the peak height ratios of ampicillin/cephalexin and cloxacillin/cephalexin over the range 10-80 micrograms/ml (ampicillin) and 5-25 micrograms/ml (cloxacillin), respectively. The sensitivity limits for ampicillin and cloxacillin in serum and urine were 5 micrograms/ml and 1 microgram/ml, respectively. Quality criteria such as accuracy, precision and specificity were studied extensively. We investigated the applicability of the HPLC assay for the developed simultaneous determination of the cumulative amounts of ampicillin and cloxacillin, excreted unchanged in urine after an oral dose containing 500 mg ampicillin and 500 mg cloxacillin to a human volunteer.

Administration, Oral↗