Penetration of cefotaxime and desacetylcefotaxime into brain abscesses in humans

Sjölin, Jan; Eriksson, N; Arneborn, P; Cars, Otto

doi:10.1128/aac.35.12.2606

Cited by 42 publications

(14 citation statements)

References 23 publications

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“…In fully developed bacterial meningitis in children and adults, both from CSF compared with that from blood originates from the slow CSF turnover and from the even slower drainage of interstitial brain fluid into CSF (8,35). Similarly, in human brain abscesses the ratio of concentrations of cefotaxime and desacetylcefotaxime in abscesses to those in plasma increased with the time interval between cefotaxime dosing and abscess fluid sampling (39).…”

Section: Discussionmentioning

confidence: 82%

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Nau

Prange

Muth

et al. 1993

Antimicrob Agents Chemother

126

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Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae.Because of its morbidity and lethality, bacterial meningitis remains a major medical concern throughout the world. The emergence of bacteria not susceptible to standard antibacterial agents in meningitis of children and immunocompromised adults has stimulated the search for alternative drugs. Broad-spectrum cephalosporins have a broad range of in vitro antibacterial activities, including that against most organisms responsible for purulent meningitis (6,7,19), and have been successfully applied as single agents for this indication in children and adults (3,9,29,34,37 Two grams of cefotaxime (Claforan; Hoechst AG, Frankfurt/M, Germany) or 2 g of ceftriaxone (Rocephin; Hoffmann-La Roche, Grenzach-Wyhlen, Germany) was infused intravenously within 30 min. Single-dose pharmacokinetics were determined after the first infusion for six patients receiving cefotaxime and six patients receiving ceftriaxone. To obtain a 24-h time course with cefotaxime, the second infusion was administered 24 h after the first dose. Thereafter, therapy was continued with 2 g three times a day or twice a day. For this reason, patients with pneumonia or fever greater than 38.5°C during the 24-h interval before the

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Section: Discussionmentioning

confidence: 82%

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Nau

Prange

Muth

et al. 1993

Antimicrob Agents Chemother

126

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“…Therapy of brain tissue infections should certainly be explored, particularly because the penetration of cephalosporins into brain tissue seems to be so poor (11,16). However, there are also implications for toxicology, because CNS excitation is a well-recognized class of adverse reaction caused by quinolones (6).…”

Section: Discussionmentioning

confidence: 99%

“…5 ,ug/ml in serum and 4.3 ,g/ml in CSF. In contrast, the penetration of ceftriaxone into brain tissue (11) and cefotaxime into brain abscesses (16) is poor and the concentrations of these drugs in brain tissue and abscesses are much lower than their concentrations in serum (e.g., <2% for ceftriaxone at 2 to 9 h after drug administration).…”

mentioning

confidence: 94%

Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve

Davey

Charter

Kelly

et al. 1994

Antimicrob Agents Chemother

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Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken from all patients; a sample of cerebrospinal fluid (CSF) uncontaminated with blood was obtained from five patients. Serum and brain tissue samples were assayed by high-pressure liquid chromatography. Drug concentrations in brain tissue exceeded those in CSF by 1.8- to 19.4-fold. Kinetic modeling suggested that peak sparfloxacin concentrations in brain tissue may have occurred later than 3 to 5 h and that actual peak concentrations may therefore have been higher (up to 10 micrograms/g of tissue). The activities of ciprofloxacin and sparfloxacin as antagonists of the gamma-aminobutyric acid antagonist (GABAA) receptor were measured with the rat vagus nerve preparation. The 50% inhibitory concentration (IC50) of ciprofloxacin was 250 microM (95.25 micrograms/ml), but in the presence of biphenyl acetic acid (BPAA), the IC50 of ciprofloxacin was only 0.6 microM (0.23 microgram/ml). In contrast, the IC50 of sparfloxacin alone or in the presence of BPAA was > 300 microM (> 100 micrograms/ml). We conclude that the concentrations of ciprofloxacin and sparfloxacin in brain tissue may exceed serum drug concentrations and cannot be predicted from the concentrations in CSF. Sparfloxacin does not have any activity as a GABA antagonist, either alone or in the presence of BPAA, at the concentrations which are likely to be reached in human brain tissue.

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“…Cefotaxime (96,175,194,195,230) into the CSF in the absence of meningeal inflammation is not lower than those of ␤-lactam antibiotics and other hydrophilic antibiotics with a similar molecular mass (177). The therapeutic index of aminoglycosides is low: because of nephro-and ototoxicity, the systemic dose of aminoglycosides can be increased in narrow limits only.…”

Section: ␤-Lactam Antibioticsmentioning

confidence: 99%

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

2010

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SUMMARY The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

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Penetration of cefotaxime and desacetylcefotaxime into brain abscesses in humans

Cited by 42 publications

References 23 publications

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

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