Reduced Release of DNA from Streptococcus pneumoniae After Treatment with Rifampin in Comparison to Spontaneous Growth and Ceftriaxone Treatment

Gerber, Joachim; Eiffert, Helmut; Fleischer, H.; Wellmer, Andreas; Munzel, U.; Nau, Roland

doi:10.1007/pl00011291

Cited by 8 publications

(4 citation statements)

References 10 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3) [44]. Bacterial protein synthesis inhibitors at concentrations above the MIC did not only inhibit LTA/TA release, but also the liberation of bacterial DNA and pneumolysin from S. pneumoniae compared to ceftriaxone [15,45].…”

Section: In Vitro Experiments Studying the Release Of Proinflammatormentioning

confidence: 91%

Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infections

Nau

Eiffert

2005

FEMS Immunology &Amp; Medical Microbiology

View full text Add to dashboard Cite

Various bacterial components (e.g., endotoxin, teichoic and lipoteichoic acids, peptidoglycans, DNA) induce or enhance inflammation by stimulating the innate immune system and/or are directly toxic in eukariotic cells (e.g., hemolysins). When antibiotics which inhibit bacterial protein synthesis kill bacteria, smaller quantities of proinflammatory or toxic compounds are released in vitro and in vivo than during killing of bacteria by beta-lactams and other cell-wall active drugs. In general, high antibiotic concentrations liberate lower quantities of bacterial proinflammatory or toxic compounds than concentrations close to the minimum inhibitory concentration. In animal models of Escherichia coli Pseudomonas aeruginosa and Staphylococcus aureus peritonitis/sepsis and of Streptococcus pneumoniae meningitis, a lower release of proinflammatory bacterial compounds was associated with a reduced mortality or neuronal injury. Pre-treatment with a bacterial protein synthesis inhibitor reduced the strong release of bacterial products usually observed during treatment with a beta-lactam antibiotic. Data available strongly encourage clinical trials comparing antibiotic regimens with different release of proinflammatory/toxic bacterial products. The benefit of the approach to reduce the liberation of bacterial products should be greatest in patients with a high bacterial load.

show abstract

Section: In Vitro Experiments Studying the Release Of Proinflammatormentioning

confidence: 91%

Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infections

Nau

Eiffert

2005

FEMS Immunology &Amp; Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…In contrast, nonbacteriolytic bactericidal antibiotics effectively inhibited the release of pneumolysin from S. pneumoniae in cultures (rifampin and clindamycin) and in rabbit CSF (rifampin). Similarly, rifampin released smaller quantities of teichoic and lipoteichoic acids and bacterial DNA from S. pneumoniae than ceftriaxone (10,26), decreased mortality in a mouse model of S. pneumoniae meningitis (20), reduced the densities of apoptotic neurons in the dentate gyrus of the hippocampal formation (P ϭ 0.005) (4), and decreased the production of reactive oxygen species by CSF phagocytes (4) in experimental rabbits.…”

Section: Fig 1 (A)mentioning

confidence: 99%

Reduced Release of Pneumolysin by Streptococcus pneumoniae In Vitro and In Vivo after Treatment with Nonbacteriolytic Antibiotics in Comparison to Ceftriaxone

Spreer¹,

Kerstan²,

Böttcher³

et al. 2003

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Pneumolysin, a virulence factor of Streptococcus pneumoniae with cytotoxic and proinflammatory activities, occurs at concentrations from 0.85 to 180 ng/ml in cerebrospinal fluid (CSF) of meningitis patients. In pneumococcal cultures and in a rabbit meningitis model, the concentrations of pneumolysin in supernatant and CSF were lower after addition of nonbacteriolytic bactericidal antibiotics (rifampin and clindamycin) than after incubation with ceftriaxone.

show abstract

“…At low antibiotic concentrations (MIC and MBC), larger quantities of LTA/TA were released than in cultures treated with 10 to 300 times the MIC of the respective antibacterial (160). Rifampin treatment resulted in less bacterial DNA release than treatment with ceftriaxone and spontaneous growth (60).…”

Section: Gram-positive Bacteriamentioning

confidence: 93%

Modulation of Release of Proinflammatory Bacterial Compounds by Antibacterials: Potential Impact on Course of Inflammation and Outcome in Sepsis and Meningitis

2002

View full text Add to dashboard Cite

SUMMARY Several bacterial components (endotoxin, teichoic and lipoteichoic acids, peptidoglycan, DNA, and others) can induce or enhance inflammation and may be directly toxic for eukaryotic cells. Bactericidal antibiotics which inhibit bacterial protein synthesis release smaller quantities of proinflammatory/toxic bacterial compounds than Β-lactams and other cell wall-active drugs. Among the Β-lactams, compounds binding to penicillin-binding protein 2 (PBP-2) release smaller amounts of bacterial substances than antibacterials inhibiting PBP-3. Generally, high antibiotic concentrations (more than 10 times the MIC) induce the release of fewer bacterial proinflammatory/toxic compounds than concentrations close to the MIC. In several in vitro and in vivo systems, bacteria treated with protein synthesis inhibitors or Β-lactams inhibiting PBP-2 induce less inflammation than bacteria treated with PBP-3-active Β-lactams. In mouse models of Escherichia coli peritonitis sepsis and of Streptococcus pneumoniae meningitis, lower release of proinflammatory bacterial compounds was associated with reduced mortality. In conclusion, sufficient evidence for the validity of the concept of modulating the release of proinflammatory bacterial compounds by antibacterials has been accumulated in vitro and in animal experiments to justify clinical trials in sepsis and meningitis. A properly conducted study addressing the potential benefit of bacterial protein synthesis inhibitors versus Β-lactam antibiotics will require both strict selection and inclusion of a large number of patients. The benefit of this approach should be greatest in patients with a high bacterial load.

show abstract

Reduced Release of DNA from Streptococcus pneumoniae After Treatment with Rifampin in Comparison to Spontaneous Growth and Ceftriaxone Treatment

Cited by 8 publications

References 10 publications

Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infections

Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infections

Reduced Release of Pneumolysin by Streptococcus pneumoniae In Vitro and In Vivo after Treatment with Nonbacteriolytic Antibiotics in Comparison to Ceftriaxone

Modulation of Release of Proinflammatory Bacterial Compounds by Antibacterials: Potential Impact on Course of Inflammation and Outcome in Sepsis and Meningitis

Contact Info

Product

Resources

About