Treatment of Gram-Negative Bacillary Meningitis in Adults

Rahal, James J.

doi:10.7326/0003-4819-77-2-295

Cited by 61 publications

(15 citation statements)

References 87 publications

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“…However, the mortality rate and rate of neurological sequelae of such infections in both children and adults remain high (5,13,17,19,25,26). Aminoglycosides have been shown to penetrate into the cerebrospinal fluid (CSF) to approximately 20% of simnultaneous serum concentrations, thus producing marginal or suboptimal antimicrobial activity in the CSF for most gram-negative bacilli.…”

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confidence: 99%

Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis

Scheld

Brown

Sande

1978

Antimicrob Agents Chemother

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Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 105 E. coli colony-forming units. The minimum bactericidal concentration was 2 ,tg/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 ± 6.0 and 20.6 ± 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity irn the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 ,ug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 ,ug of netilmicin per ml as compared to 14.1

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Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis

Scheld

Brown

Sande

1978

Antimicrob Agents Chemother

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“…Antibiotic susceptibility of these pathogens is often limited to chloramphenicol and aminoglycosides. When chloramphenicol susceptibility is known, this drug has been favored as the treatment of choice because of its greater penetrability from serum to cerebrospinal fluid (11 and an inoculum of 105 organisms per ml. One-half milliliter of inoculum was added to 0.5 ml of each antibiotic dilution, and the suspensions were incubated for 18 h at 370C.…”

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Bactericidal and Bacteriostatic Action of Chloramphenicol Against Meningeal Pathogens

Rahal

Simberkoff

1979

Antimicrob Agents Chemother

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160

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The bacteriostatic and bactericidal effects of chloramphenicol, ampicillin, tetracycline, and sulfisoxazole were compared against several potential meningeal pathogens. Chloramphenicol is bactericidal at clinically achievable concentrations against Haemophilus influenzae, Streptococcuspneumoniae, and Neisseria meningitidis. It is bacteriostatic against gram-negative bacilli of the farnily Enterobacteriaceae and against Staphylococcus aureus. Chloramphenicol has proven highly efficacious in the treatment of bacterial meningitis caused by those organisms against which it is bactericidal at low concentrations. Because leukocytic phagocytosis in the subarachnoid space is inefficient, we propose that bactericidal activity in cerebrospinal fluid is important for optimal therapy of bacterial meningitis. Chloramphenicol does not provide such activity in meningitis caused by enteric gram-negative bacilli.Chloramphenicol has assumed an increasingly important role in the therapy of pyogenic meningitis. It is considered the drug of choice for meningitis due to ampicillin-resistant Haemophilus influenzae and for pneumococcal and meningococcal meningitis in patients allergic to penicillin. Recently, enteric gram-negative bacfilary meningitis has been noted more frequently among adults undergoing neurosurgical procedures and in those with debilitating disease (7). Antibiotic susceptibility of these pathogens is often limited to chloramphenicol and aminoglycosides. When chloramphenicol susceptibility is known, this drug has been favored as the treatment of choice because of its greater penetrability from serum to cerebrospinal fluid (11 and an inoculum of 105 organisms per ml. One-half milliliter of inoculum was added to 0.5 ml of each antibiotic dilution, and the suspensions were incubated for 18 h at 370C. The minimal inhibitory concentration (MIC) was defined as the lowest concentration of antibiotic preventing visible turbidity. All clear tubes were subcultured with a calibrated loop (0.01 ml) onto antibiotic-free agar for 18 h at 37°C. The minimal bactericidal concentration (MBC) was defined as that yielding growth of fewer than five colonies (>99% killing). Supplement C (2.5%, Difco) was added for determination of H. influenzae susceptibility. Quantitative studies of bacterial killing rates were performed with 2-mi suspensions containing 105 organisms per ml. Aliquots of 0.1 ml were removed at timed intervals, and colony-forming units were counted by the standard plate dilution technique. RESULTSEleven strains of H. influenzae, 10 strains of S. pneumoniae, and 10 strains ofN. meningitidis were tested for their bacteriostatic and bactericidal susceptibility to chloramphenicol, ampicillin, and tetracycline. Susceptibility of the N. meningitidis strains to sulfisoxazole was also tested.Against H. influenzae, the MIC of chloramphenicol was at least twofold lower than that of ampicillin for 10 of 11 strains. The MBC of chloramphenicol was at least twofold lower than that of ampicillin for six strains and equal to that of ampic...

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“…Clearance of the micro-organisms from the meninges is facilitated by chemotherapeutic and antimicrobial agents which inhibit multiplication and kill the bacteria enhancing their removal by the host. Failure to achieve a therapeutic level may explain many treatment failures, since antibiotics vary greatly in their ability to penetrate the 'bloodbrain barrier' (Rahal, 1972;McCracken, 1974), and even with the same agent, penetration of this barrier varies tremendously with the course of the meningitis (McCracken, 1974;Smith, 1973).…”

Section: Methodsmentioning

confidence: 99%

Intrathecal antibiotic therapy for neonatal meningitis.

Yeung¹

1976

Archives of Disease in Childhood

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Treatment of Gram-Negative Bacillary Meningitis in Adults

Cited by 61 publications

References 87 publications

Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis

Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli Meningitis

Bactericidal and Bacteriostatic Action of Chloramphenicol Against Meningeal Pathogens

Intrathecal antibiotic therapy for neonatal meningitis.

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