Diffusion of cloxacillin into synovial tissue.

Mattie, H.; Marie, S. de; Slaghuis, G; Rozing, P. M.; Strijen, E. Van

doi:10.1111/j.1365-2125.1992.tb04138.x

Cited by 6 publications

(4 citation statements)

References 5 publications

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“…[1][2][3] Cloxacillin peak serum concentrations can reach up to 287 mg/L after 20 minutes of 2 g intravenous (i.v.) [1][2][3] Cloxacillin peak serum concentrations can reach up to 287 mg/L after 20 minutes of 2 g intravenous (i.v.)…”

Section: Introductionmentioning

confidence: 99%

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Cloxacillin‐induced seizure in a hemodialysis patient

Nekidy

Dziamarski

Soong

et al. 2015

Hemodialysis International

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We are reporting a cloxacillin-induced seizure in a patient with stage 5 chronic kidney disease requiring hemodialysis. To our knowledge, there are no published case reports of seizures induced by parenteral cloxacillin in hemodialysis patients. A young hemodialysis female was admitted to the hospital with decreased level of consciousness. Blood cultures revealed methicillin-sensitive Staphylococcus aureus where cloxacillin 2 g intravenously every 4 hours was initiated. Head computed tomography (CT) was not significant. After 14 hours of cloxacillin therapy (4 doses), the patient demonstrated tonic/clonic seizure activity, where phenytoin and lorazepam were initiated. The anti-seizure medications partially reduced seizure activity. Once the cloxacillin was discontinued, the seizures stopped. Two weeks later, all anti-seizure medications were stopped with no further seizure activity. Cloxacillin elimination in hemodialysis patients is similar to patients with normal kidney function. Although cloxacillin does not significantly cross the blood-brain barrier, the correlation between the start of seizures and cloxacillin initiation was confirmed by the negative CT and blood chemistry laboratory results. Moreover, seizure activity was terminated upon discontinuation of cloxacillin. Although further investigation for the cause of such seizures is warranted, clinicians should use caution when giving high doses of cloxacillin in hemodialysis patients.

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Section: Introductionmentioning

confidence: 99%

“…Cloxacillin, a beta-lactam, isoxazolyl penicillin with narrow spectrum activity and is an ideal agent to treat Staphylococcus aureus infections. [1][2][3] Cloxacillin peak serum concentrations can reach up to 287 mg/L after 20 minutes of 2 g intravenous (i.v.) infusion and a minimum concen-tration of 2.7 mg/L within 4 hours post-infusion.…”

Section: Introductionmentioning

confidence: 99%

Cloxacillin‐induced seizure in a hemodialysis patient

Nekidy

Dziamarski

Soong

et al. 2015

Hemodialysis International

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“…In three of those patients the albumin quotient was normal or slightly elevated and the steady-state CCSF/Cu ratio was similar to the predicted normal value. 7 These findings indicate that eradicating staphylococci from CSF in cases of meningitis with a low degree of inflammation may be difficult. …”

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confidence: 96%

The passage of cloxacillin into cerebrospinal fluid in the absence of meningitis.

Schievink

Mattie

Thomeer

et al. 1993

Brit J Clinical Pharma

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1 Eleven patients undergoing lumbar discectomy received cloxacillin by continuous i.v. infusion, starting before the operation. During the operation several blood samples and one CSF sample were taken.2 Mean rate constants describing the passive transfer of drug from plasma to CSF (kp) and the largely active transfer in the opposite direction (kcsF) were estimated. 3 In some subjects the CSF albumin quotient, defined as the ratio between the albumin concentration in CSF and in plasma times 1000, was slightly elevated (up to 23) which caused a significant increase in the value of kp. 4 The estimate of mean kp for healthy individuals was 0.065 h-1, which corresponds to a half-life of 10 h. The estimate of mean kcsF was 2.10 h-'. This predicts a steadystate CSF drug concentration which is 3% of the unbound plasma drug concentration. 5 There was a significant lag between the time courses of plasma and CSF drug concentrations, presumably reflecting the time for drug to move from the choroid plexus to the lumbar sampling site. 6 Four other patients received cloxacillin for prophylactic or therapeutic reasons by continuous i.v. infusion. In three of those patients the albumin quotient was normal or slightly elevated and the steady-state CCSF/Cu ratio was similar to the predicted normal value. 7 These findings indicate that eradicating staphylococci from CSF in cases of meningitis with a low degree of inflammation may be difficult.

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“…The relationship between unbound plasma and tissue concentrations can be described adequately by rate constants for diffusion into an out of tissue. In many tissues studied so far, in animals [6] and in man [7,10], the distribution between tissue and plasma is relatively rapid. This explains why in experimental infections unbound plasma concentrations can be compared satisfactorily with those in vitro, although the shape of the concentration curve in the tissue is somewhat different from that in plasma.…”

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confidence: 99%

The importance of pharmacokinetics and pharmacodynamics for effective treatment of infections

Mattie

1993

Clin Investig

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As soon as they were introduced, the pharmacokinetics of antibiotics became a subject of interest. There are two reasons for this. First, the relationship between concentration and antibacterial effect can easily be established in vitro, and, second, plasma concentrations in patients can be measured relatively easily by bioassay. This led to early insight into the relationship between in vivo pharmacokinetics and effective concentrations in vitro. For instance, the very rapid excretion of penicillin by the kidney was perceived soon after introduction of this drug, the corollary of this finding being that effective concentrations in the body can be maintained for only a short period after administration. For this reason the very low doses of penicillin administered at that time were given frequently, even continuously. Pharmacokinetics as a science has progressed since those early days, but it remains to be seen whether this has also led to a more rational approach to antibiotic dosages. The intention of this short review is not to discuss all possible aspects of the pharmacokinetics of antibiotics but rather to consider those that are relevant to the clinical administration of antibiotics on the basis of their pharmacodynamics.The most common parameter of the efficacy of antibiotics in vitro is the minimal inhibitory concentration (MIC), sometimes supplemented by the minimal bactericidal concentration. However, although the MIC is very useful for simple screening as well as decision making in clinical practice, it does not lead to an understanding of the relationship between a range of concentrations and effects in time. Moreover, it has become apparent that the effect of the antibiotic at the MIC should not be regarded as either the minimal antibacterial effect -not even in vitro -or the maximal effect. A more relevant parameter of the relationship between concentration and effect is the killing rate, or the rate of the inhibition of growth of the bacteria, because this is a continuous variable dependent on concentration. This parameter can indeed be quantified in terms of potency and efficacy; in this terminology, potency defines the concentration range within which the antibacterial effect increases from zero to maximal, and efficacy indicates the magnitude of the maximal bacteriostatic or bactericidal effect itself. Another pharmacodynamic parameter, which is particularly important for gram-positive bacteria, is the postantibiotic effect. This considers that, at least in vitro, inhibition of bacterial growth continues for some time after the antibiotic has been removed from the medium [2]. This phenomenon is not limited to the field of antibiotics, and in pharmacological terminology it has been known for some time under the name of hysteresis.Present knowledge of the relationship between concentration and effect in time results from research that has focused on beta-lactam antibiotics and aminoglycosides. Beta-lactam antibiotics are characterized by a steep concentration-effect curve in vitro [9], which means...

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Diffusion of cloxacillin into synovial tissue.

Cited by 6 publications

References 5 publications

Cloxacillin‐induced seizure in a hemodialysis patient

Cloxacillin‐induced seizure in a hemodialysis patient

The passage of cloxacillin into cerebrospinal fluid in the absence of meningitis.

The importance of pharmacokinetics and pharmacodynamics for effective treatment of infections

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