Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges

Bakken, Johan S.; Bruun, Johan N.; Gaustad, Peter; Tasker, Tim

doi:10.1128/aac.30.3.481

Cited by 29 publications

(11 citation statements)

References 15 publications

(16 reference statements)

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“…In contrast, the combination of piperacillin with tazobactam produced bactericidal activity in the CSF in vivo at all dosages that were investigated ( Piperacillin (80) 6 0.45 ± 0.29 2 (6) Piperacillin (200) 6 0.53 ± 0.10 3 (8) Tazobactam ( (20,23) and for sulbactam in the infected CSF of rabbits (10) and humans (9). In contrast, concentrations of clavulanic acid in human infected CSF are low, as a result of modest penetration and dosage limitations in patients (2,5).…”

Section: Resultsmentioning

confidence: 99%

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase

Leleu

Kitzis

Vallois

et al. 1994

Antimicrob Agents Chemother

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We evaluated the pharmacokinetics and therapeutic elficacies of piperacillin and tazobactam, a j-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of KlebsieUla pneumoniae producing the TEM-3 extended-spectrum P-lactamase.Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20%o of the total dose. The mean (± standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 ± 3.9% 1for piperacillin given alone and 36.3 ± 21.9%o for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at'dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 0.34 and -0.73 ± 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kglh) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 ± 0.35 log CFU/ml/h). The study shows that ta?obactam is able to provide eflective protection' against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various P-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum P-lactamases.Gram-negative bacilli producing ,B-lactamases that hydrolyze extended-spectrum cephalosporins have been identified since 1983 (17, 22). Nosocomial infections due to members of the family Enterobacteriaceae that produce these extendedspectrum 13-lactamases have been observed in studies from a number of institutions, predominantly in Europe (3,14,16,18). Therefore, neonatal or neurosurgery-associated meningitis caused by enteric bacilli producing such ,B-lactamases is likely to occur in the future. Antimicrobial chemotherapy of serious infections caused by these organisms is difficult, and novel regimens must be investigated with animal models. On an in vitro basis, the combination of a P-lactam derivative with a 1-lactamase inhibitor is one of the few available options. Tazobactam is a ,B-lactamase inhibitor recently introduced in the clinical setting. In vitro, a combination of tazobactam and piperacillin has been found to be promising against ,1-lactamase-producing members of the Enterobacteriaceae (1, 11-13). In a model of meningitis caused by a strain of Escherichia coli producing the TEM-1 f-lactamase, the standard 8:1 ratio of piperacillin to tazobactam was found to be moderately effective, but other ratios were not investigated (15). Using the same well-standardized rabbit model, we evaluated (i) the kinetics and efficacies of piperacillin and tazobactam, given alone or in combination, in the cerebrospinal fluid (CSF) of rabbits with meningitis due...

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Section: Resultsmentioning

confidence: 99%

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase

Leleu

Kitzis

Vallois

et al. 1994

Antimicrob Agents Chemother

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“…13 Amoxicillinclavulanic acid has been shown to be associated with a higher rate of relapse, but the combination remains an alternative oral agent in Thailand. 3,13 This is not an acceptable option, however, for treatment of neurologic melioidosis because the concentration of amoxicillin-clavulanic acid in CSF is < 10% relative to blood, 14 which falls below the MIC for B. pseudomallei. 15 Patient 2 had relapse while being treated with amoxicillin-clavulanic acid, and patient 3 had relapse 5 months after completing 20 weeks of oral treatment, 16 weeks of which was with amoxicillin-clavulanic acid.…”

Section: Discussionmentioning

confidence: 99%

Variable Presentation of Neurological Melioidosis in Northeast Thailand

Limmathurotsakul¹,

Chaowagul²,

Wongsrikaew³

et al. 2007

The American Journal of Tropical Medicine and Hygiene

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“…An alternative approach for the treatment of meningitis due to such organisms is the use of a penicillin derivative combined with an agent that inhibits the 1-lactamase elaborated by the infecting organism. Limited data on cerebrospinal fluid (CSF) penetration and efficacy of such combinations in experimental animals and humans are available (3,5,9,14,24,28). Using a well-standardized rabbit model, we studied the pharmacokinetics and therapeutic efficacy of a novel P-lactamase inhibitor, tazobactam (CL 298,741; formerly YTR 830), combined with piperacillin, a broad-spectrum acylureido-penicillin, in experimental meningitis due to a ,-lactamase-producing strain of Escherichia coli.…”

mentioning

confidence: 99%

Evaluation of piperacillin-tazobactam in experimental meningitis caused by a beta-lactamase-producing strain of K1-positive Escherichia coli

Kern

Kennedy

Sachdeva

et al. 1990

Antimicrob Agents Chemother

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We evaluated the pharmacokinetics and therapeutic efficacy of piperacillin combined with tazobactam, a novel P-lactamase inhibitor, in experimental meningitis due to a I-lactamase-producing strain of Kl-positive Escherichia coli. Different doses of piperacillin and tazobactam, as single agents and combined (8:1 ratio; dosage range, 40/5 to 200/25 mg/kg per h), and of ceftriaxone were given to experimentally infected rabbits by intravenous bolus injection followed by a 5-h constant infusion. The mean (+ standard deviation) rates for penetration into the cerebrospinal fluid of infected animals after coadministration of both drugs were 16.6 _ 8.4% for piperacillin and 32.5 ± 12.6% for tazobactam. Compared with either agent alone, combination treatment resulted in significantly better bactericidal activity in the cerebrospinal fluid. The bactericidal activity of piperacillin-tazobactam was dose dependent: cerebrospinal fluid bacterial titers were reduced by 0.37 ± 0.19 log1o CFU/ml per h with the lowest dose versus 0.96 ± 0.25 log1o CFU/ml per h with the highest dose (P < 0.001). At the relatively high doses of 160/20 and 200/25 mg of piperacillin-tazobactam per kg per h, the bactericidal activity of the combination was comparable to that of 10 and 25 mg of ceftriaxone per kg per h, respectively.

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Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges

Cited by 29 publications

References 15 publications

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase

Variable Presentation of Neurological Melioidosis in Northeast Thailand

Evaluation of piperacillin-tazobactam in experimental meningitis caused by a beta-lactamase-producing strain of K1-positive Escherichia coli

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