The Absorption Into and Distribution of Penicillin in the Cerebrospinal Fluid

Dumoff-Stanley, Edith; Dowling, Harry F.; Sweet, Lewis K.

doi:10.1172/jci101692

Cited by 30 publications

(4 citation statements)

References 11 publications

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“…Penetration of penicillin into the CSF and other foci of infection has been studied since the introduction of this antimicrobial agent into clinical use [24]. The chemical characteristics of penicillin are major factors limiting its entry into the CSF [25].…”

Section: Discussionmentioning

confidence: 99%

Intermittent or Continuous Therapy of Experimental Meningitis Due to Streptococcus pneumoniae in Rabbits: Preliminary Observations on the Postantibiotic Effect in Vivo

Sande¹,

Korzeniowski²,

Allegro³

et al. 1981

Clinical Infectious Diseases

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The relative effectiveness of bolus vs. constant intravenous administration of equivalent doses of penicillin G in killing bacteria in vivo was studied in a rabbit model of meningitis due to Streptococcus pneumoniae. Samples of cerebrospinal fluid (CSF) and serum were obtained from 30 rabbits at intervals of~8 hr after treatment for determination of antibiotic concentrations and titers of viable bacteria in the CSF. When penicillin G was given by continuous infusion (105 units/hr after an initial lOS-unit loading dose), concentrations of drug in serum and CSF reached a steady state in 1 hr. With intermittent bolus administration of 4 x 105 units every 4 hr, higher peak and lower trough concentrations were achieved, and these concentrations paralleled those in the CSF. Although an initial acceleration in bactericidal rate was observed with the bolus infusion between the first and second hour of therapy, after the second hour the rate of bacterial killing was identical for the two methods of administration. The duration of therapy required for sterilization of the CSF was dependent only on the bacterial count before treatment and not on the mode of drug administration. The effect of single bolus intravenous administration of ampicillin was examined in experimental pneumococcal meningitis. Ampicillin was given at various dosages (3.25-62.5 mg/kg), and frequent samples of CSF were obtained for determination of concentrations of pneumococci and ampicillin. A long postantibiotic effect was observed in the CSF of all animals, and this effect consistently was longer than that observed in vitro.The question of the most effective mode of administration of (3-lactam antibiotics for treatment of severe bacterial infections is controversial. Commonly used regimens are largely empirical and are based on pharmacokinetic parameters (often only available from studies done with normal volunteers), knowledge of susceptibility characteristics of the suspected pathogen, and tradition. Parenteral therapy is preferred, but unpredictable absorption (e.g., shock) and clotting abnormalities may make the im route unreliable. Continuous iv administration produces a relatively fixed concentration of the antibiotic over time. Intermittent, or bolus, administration produces high initial con-

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Section: Discussionmentioning

confidence: 99%

Intermittent or Continuous Therapy of Experimental Meningitis Due to Streptococcus pneumoniae in Rabbits: Preliminary Observations on the Postantibiotic Effect in Vivo

Sande¹,

Korzeniowski²,

Allegro³

et al. 1981

Clinical Infectious Diseases

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“…It seems, however, clear that different substances behave differently. For instance, the passage of labelled sodium and penicillin into the ventricular spaces appears to be greater than into the subarachnoidal space (Dumoff-Stanley, Dowling & Sweet, 1946;Sweet, Selverstone, Solomon & Backay, 1949), whereas the reverse is true for nitrous oxide (Bessman, Alman, Hayes & Fazekas, 1952). Labelled albumin also was found in greater concentration in the c.s.f.…”

Section: Discussionmentioning

confidence: 99%

Passage of circulating adrenaline into perfused cerebral ventricles and subarachnoidal space

Draskoci¹,

Feldberg²,

Haranath³

1960

The Journal of Physiology

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“…The zone of inhibition was then plotted against the logarithm of the antibiotic concentration, and the results were used to generate a computer program for the calculation of unknowns by the method of least squares. For ex- (3,6,13,18,30).…”

Section: Methodsmentioning

confidence: 99%

Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges

Beam

Allen

1977

Antimicrob Agents Chemother

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Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.

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The Absorption Into and Distribution of Penicillin in the Cerebrospinal Fluid

Abstract: The slow excretion of penicillin from the cerebrospinal fluid into the blood stream (Figure 1).

Cited by 30 publications

References 11 publications

Intermittent or Continuous Therapy of Experimental Meningitis Due to Streptococcus pneumoniae in Rabbits: Preliminary Observations on the Postantibiotic Effect in Vivo

Intermittent or Continuous Therapy of Experimental Meningitis Due to Streptococcus pneumoniae in Rabbits: Preliminary Observations on the Postantibiotic Effect in Vivo

Passage of circulating adrenaline into perfused cerebral ventricles and subarachnoidal space

Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges

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