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

Schievink, H. I.; Mattie, H.; Thomeer, R.T.W.M.; Strijen, E. Van

doi:10.1111/j.1365-2125.1993.tb05892.x

Cited by 14 publications

(4 citation statements)

References 10 publications

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“…A CRP measurement was not available at the first visit; (2) our patient was much older than previously described successfully treated patients; (3) Immune-mediated transverse myelitis is possible, although there was no response to high-dose IV methylprednisolone; and (4) Cloxacillin has poor lipid solubility and CSF penetration may be insufficient. 17 Furthermore, poor penetration of cloxacillin into abscesses of the central nervous system has been previously described. 18 Failure of IV crystalline penicillin was also noted in a previous report of MSSA myelitis, 12 supporting the hypothesis that penicillins may be a poor choice as monotherapy for bacterial myelitis.…”

Section: Staphylococcus Aureus Myelitis S Karakonstantis Et Almentioning

confidence: 99%

A rare case of acute transverse myelitis associated with Staphylococcus aureus bacteremia and osteomyelitis

Karakonstantis

Galani

Maragou

et al. 2017

Spinal Cord Ser Cases

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INTRODUCTION: Direct intramedullary infections are considered very rare. Only few reports of Staphylococcus aureus myelitis have been published. CASE PRESENTATION: Our patient, a 79-year-old male, presented with a 2-day history of high-grade fever and high inflammatory markers and progressively developed tetraplegia during hospitalization. Lumbar puncture revealed cerebrospinal fluid pleocytosis and a spinal cord MRI revealed transverse myelitis at the level of C3-C5 and possible osteomyelitis of C5-T1. Two blood cultures were positive for methicillin-sensitive S. aureus. Despite control of the infection, there was no neurologic improvement. DISCUSSION: The morbidity of infectious myelitis can be severe. Considering the rarity of S. aureus myelitis, experience gained from case reports is important. A brief review of the available literature is provided.

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Section: Staphylococcus Aureus Myelitis S Karakonstantis Et Almentioning

confidence: 99%

A rare case of acute transverse myelitis associated with Staphylococcus aureus bacteremia and osteomyelitis

Karakonstantis

Galani

Maragou

et al. 2017

Spinal Cord Ser Cases

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“…Le Turnier et al reported lower median (IQR) CSF:plasma ratios and steady state CSF concentrations of 1.8% (1.7%–2.8%) and 0.66 (0.5–0.9) mg/L, respectively, with cloxacillin 12 g IV daily compared with cefazolin [ 7 ]. A 3% ratio of CSF:unbound plasma concentration for cloxacillin has been estimated by others [ 26 ]. Flucloxacillin 2000 mg IV every 4 hours resulted in CSF concentrations of 0.3 mg/L, and others report very low CSF concentrations even when utilizing continuous infusions [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Evaluation of Cefazolin in the Cerebrospinal Fluid of Critically Ill Patients

Novak

Kršák

Kiser

et al. 2021

Open Forum Infectious Diseases

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Background The relative distribution of cefazolin into the cerebrospinal fluid (CSF) remains debated. Determining the distribution of cefazolin to the CSF in non-infected adults may allow for further treatment applications of cefazolin. This prospective pharmacokinetic study aimed to determine the pharmacokinetic parameters of cefazolin in serum and CSF from external ventricular drains (EVD) in neurologically injured adults. Methods Blood and CSF was collected, using a biologic waste protocol, for cefazolin quantification and trapezoidal rule based pharmacokinetic analysis in a total of 15 critically ill adults receiving 2000mg IV every 8 hours or the renal dose equivalent for EVD prophylaxis. Results A median of 3 blood (range 2-4) and 3 CSF (range 2-5) samples were collected in each patient. The most common admitting diagnosis was subarachnoid hemorrhage (66.7%). Median calculated cefazolin CSF Cmax and Cmin (IQR) were 2.97mg/L (1.76-8.56) and 1.59mg/L (0.77-2.17), respectively. Median (IQR) CSF to serum area under-the-curve ratio was 6.7% (3.7%-10.6%), with time matched estimates providing a similar estimate (8.4%). Of those receiving cefazolin every 8 hours, the median and minimum directly measured CSF cefazolin concentration 4 hours or greater following administration were 1.87 and 0.78 mg/L, respectively. Conclusion Cefazolin dosed for EVD prophylaxis achieved CSF concentrations suggesting viability as a therapeutic option for patients with meningitis or ventriculitis due to susceptible bacteria such as methicillin-susceptible Staphylococcus aureus. Further clinical trials are required to confirm a role in therapy for cefazolin. Population-based pharmacokinetic-pharmacodynamic modeling may suggest an optimal cefazolin regimen for the treatment of central nervous system infections.

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“…Penetrates in CSF of inflamed meninges to a limited extent, therefore higher doses may be necessary to attain therapeutic targets [106]. Furthermore, therapy failure has been described in patients under treatment for Staphylococcus meningitis [107].…”

Section: Cloxacillinmentioning

confidence: 99%

“…Penetrates in CSF of inflamed meninges to a limited extent, therefore higher doses may be necessary to attain therapeutic targets [106].…”

Section: Flucloxacillinmentioning

confidence: 99%

Pharmacokinetics of Antimicrobials in Children with Emphasis on Challenges Faced by Low and Middle Income Countries, a Clinical Review

et al. 2022

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Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism and excretion). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. Additionally, there are significant logistical constraints to therapeutic drug monitoring that further emphasize the importance of understanding pharmacokinetics and dosing in LMIC. Both malnutrition and diarrheal disease reduce the extent of enteral absorption. Multiple antiretrovirals and antimycobacterial agents, commonly used by children in low resource settings, have potential interactions with other antimicrobials. Hypoalbuminemia, which may be the result of malnutrition, nephrotic syndrome or liver failure, increases the unbound concentrations of protein bound drugs that may therefore be eliminated faster. Kidney function develops rapidly during the first years of life and different inflammatory processes commonly augment renal clearance in febrile children, potentially resulting in subtherapeutic drug concentrations if doses are not adapted. Using a narrative review approach, we outline the effects of growth, maturation and comorbidities on maturational and disease specific effects on pharmacokinetics in children in LMIC.

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

Cited by 14 publications

References 10 publications

A rare case of acute transverse myelitis associated with Staphylococcus aureus bacteremia and osteomyelitis

A rare case of acute transverse myelitis associated with Staphylococcus aureus bacteremia and osteomyelitis

Pharmacokinetic Evaluation of Cefazolin in the Cerebrospinal Fluid of Critically Ill Patients

Pharmacokinetics of Antimicrobials in Children with Emphasis on Challenges Faced by Low and Middle Income Countries, a Clinical Review

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