Relation of Concentrations of Bacteria and Bacterial Antigen in Cerebrospinal Fluid to Prognosis in Patients with Bacterial Meningitis

Feldman, William E.

doi:10.1056/nejm197702242960806

Cited by 163 publications

(68 citation statements)

References 15 publications

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“…At an equivalent rate of bacterial killing, 500/0 of animals with higher initial titers (> 10 5 cfu/ml) still had detectable bacterial counts in the CSF at the end of the experiment. A similar observation on the role of initial bacterial titers was made by Feldman [28], who studied humans with meningitis. A higher rate of complications and a slower response to therapy was seen in patients with meningitis whose bacterial titers before treatment exceeded 10 7 cfu/ml as compared with the response of patients who had lower CSF titers.…”

Section: Discussionsupporting

confidence: 66%

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: Discussionsupporting

confidence: 66%

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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“…This is particularly true in regard to the contribution of bacterial components to the induction of the host inflammatory response once bacteria gain access to the cerebrospinal fluid (CSF). An understanding of which bacterial component(s) incites the host response is important since products of inflammation that are released during infection may injure host tissues and be detrimental to the recovery from disease [1][2][3]. This information may provide important clues as to why mortality from pneumococcal disease remains at 20070 despite the development of new, highly bactericidal antibiotics [4].…”

mentioning

confidence: 99%

The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis

Tuomanen¹,

Tomasz²,

Hengstler³

et al. 1985

Journal of Infectious Diseases

222

176

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The relative contribution of bacterial components to the induction of inflammation during Streptococcus pneumoniae meningitis is unknown. Several strains of pneumococci with differences in cell surface characteristics (capsule or cell wall) were compared for the effect on the inflammatory response evoked during infection of the cerebrospinal fluid (CSF) in vivo. The presence of bacterial capsular polysaccharide was not necessary for bacterial growth in CSF in vivo but correlated with greater CSF bacterial density. CSF inflammatory changes began to appear when the bacterial concentration exceeded 10 5 cfu/ml, regardless of the pneumococcal strain. CSF inflammatory changes could be invoked by cisternal instillation of 10 5-106 cell equivalents of whole, heat-killed unencapsulated strains or their isolated cell walls but not by similar concentrations of heat-killed encapsulated strains or isolated capsular polysaccharide. Hypoglycorrhachia was observed only during inflammation caused by live bacteria. The inflammatory response characteristic of naturally acquired pneumococcal meningitis can be reproduced by challenge with both encapsulated and unencapsulated bacteria. The bacterial cell wall appears to be the most potent pneumococcal surface component in inducing CSF inflammation.

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“…They may have been detecting whole, dead gonococci, fragments of the cell wall capsule (28), or intracellular constituents. In reference to the techniques used, Feldman has shown that the sensitivity of countercurrent immunoelectrophoresis in detecting bacterial antigens may be limited by small concentrations of bacteria (29). Thus, the present methodology for antigen study may have been too insensitive for N gonorrhea.…”

Section: Discussionmentioning

confidence: 98%

Survey for immune complexes in disseminated gonococcal arthritis‐dermatitis syndrome

Ludivico

Myers

1979

Arthritis & Rheumatism

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Seventeen patients with characteristic disseminated gonococcal arthritis-dermatitis syndrome were studied for the presence of immune complexes, and circulating gonococcal antigen and antibody. The two immune complex techniques, monoclonal rheumatoid factor assay and cryoglobulin survey, did not reveal any consistent abnormalities. Complement levels (CH50, C'3, C'4) were not consistent with peripheral consumption except in 2 patients with coinciding systemic lupus erythematosus. Gonococcal antibody was detected in 47% of patients when they presented with the syndrome. However, gonococcal antigen was not found in either serum or synovial fluid. These results do not support the hypothesis that circulating immune complexes are involved in the pathogenesis of disseminated gonococcal arthritis-dermatitis syndrome.The pathogenesis of the inflammatory lesions in disseminated gonococcal syndrome has been poorly understood and controversial. Various theories have been proposed to explain the skin and joint manifestations. The current explanation for the skin lesions has been

show abstract

Relation of Concentrations of Bacteria and Bacterial Antigen in Cerebrospinal Fluid to Prognosis in Patients with Bacterial Meningitis

Cited by 163 publications

References 15 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

The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis

Survey for immune complexes in disseminated gonococcal arthritis‐dermatitis syndrome

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