Treatment of Pneumococcal Pneumonia with Penicillin

Meads, Manson; Harris, H. W.; Finland, Maxwell; Wilcox, Clare

doi:10.1056/nejm194506282322601

Cited by 31 publications

(21 citation statements)

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“…Administration of penicillin for 8 hr by either the continuous or intermittent mode resulted in similar outcomes 6.0 (table 1). Ten of 15 rabbits receiving continuous infusions of penicillin as well as 11 of 15 rabbits treated with intermittent boluses of penicillin had sterile CSF after 8 hr of treatment.…”

Section: Duration Of Therapy (Hrs)mentioning

confidence: 83%

“…For purposes of comparison, the postantibiotic effect was defined as the interval from the time when concentrations of ampicillin in CSF first dropped below 0.1 Jig/ml (the MIC of the test strain) until bacterial titers in CSF were loglo 1.0 cfu/ml higher than the bacterial concentration achieved at the nadir of the curve. The duration of the initial decline in bacterial titer was variable (1)(2)(3)(4)(5)(6) hr) and did not correlate with peak concentrations of ampicillin in CSF. The second, static phase also varied so that the total duration of the postantibiotic effect was [6][7][8][9][10][11][12] hr.…”

Section: Duration Of Therapy (Hrs)mentioning

confidence: 95%

“…The duration of the initial decline in bacterial titer was variable (1)(2)(3)(4)(5)(6) hr) and did not correlate with peak concentrations of ampicillin in CSF. The second, static phase also varied so that the total duration of the postantibiotic effect was [6][7][8][9][10][11][12] hr. Two of three animals that received the highest dose of ampicillin (62.5 mg/kg) had sterile CSF after 4-6 hr and were presumed "cured".…”

Section: Duration Of Therapy (Hrs)mentioning

confidence: 95%

“…However, clinical experience suggests that administration of these large doses may not be necessary. Pneumococcal pneumonia can be cured with only 8 x 10 3 to 1.2 X 10 4 units of penicillin G given every 12 hr [6], despite concentrations of drug in tissue below the MIC. Cure of scarlet fever has occurred when penicillin was detectable in the serum for only 6 hr per day [7].…”

mentioning

confidence: 99%

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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: Duration Of Therapy (Hrs)mentioning

confidence: 83%

Section: Duration Of Therapy (Hrs)mentioning

confidence: 95%

Section: Duration Of Therapy (Hrs)mentioning

confidence: 95%

mentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…Experience has shown, however, that a clinical and bacteriological cure can be achieved with a drug regimen that does not maintain the MIC throughout the entire dosage interval. Kinetic analysis of early experience in the treatment of pneumococcal pneumonia with 8,000 to 12,000 U of penicillin G given every 12 h (12) indicates that a drugfree period occurred with such regimens. Eagle et al (2) recognized this fact and developed animal models which confirmed the clinical observation that penicillin therapy was effective when tissue concentrations dropped below the MIC for part of the dosage interval.…”

mentioning

confidence: 99%

Enhancement of leukocyte activity against Escherichia coli after brief exposure to chloramphenicol

Pruul

McDonald

1979

Antimicrob Agents Chemother

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The effect of brief exposure of Escherichia coli to chloramphenicol on the antibacterial activity of normal human leukocytes was studied by following changes in viability of the bacteria in the presence of leukocytes and serum. Growth was suppressed, and the extent of suppression was directly related to the period of exposure and the concentration of chloramphenicol. When exposed to clinically achievable levels of the drug for 10 min, E. coli failed to resume normal growth for 1 to 4 h in the presence of leukocytes and serum after removal of the drug. The post-antibiotic leukocyte enhancement effect required the presence of antibody and complement. This effect demonstrates the importance of early events in the encounter between antibiotic and microorganism in determining the subsequent activity of host defense components.

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Pneumo Nia in the Aged

Zeman¹

1946

Arch Intern Med (Chic)

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Treatment of Pneumococcal Pneumonia with Penicillin

Cited by 31 publications

References 0 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

Enhancement of leukocyte activity against Escherichia coli after brief exposure to chloramphenicol

Pneumo Nia in the Aged

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