Lack of synergism of ampicillin and gentamicin in experimental listeriosis

Hof, Herbert; Gückel, H.

doi:10.1007/bf01646117

Cited by 28 publications

(8 citation statements)

References 15 publications

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“…Gentamicin was rapidly bactericidal against extracellular L. monocytogenes, and its use in patients with bacteremia with multiple visceral involvement appears to be fully justified. The synergy of the amoxicillin-gentamicin combination, which is one of the bacteriological bases for the reference treatment of neonatal listeriosis and Listeria meningitis, was not observed during intracellular infection of HeLa cells, nor was it observed in the experimental animal model of L. monocytogenes infection (12). Imipenem alone or in combination with gentamicin was only weakly bactericidal in an experimental model of L. monocytogenes infections in newborn rats, despite the very low MIC of this drug (14).…”

Section: Resultsmentioning

confidence: 96%

“…The recommended treatment for listeriosis remains amoxicillin alone or combined with gentamicin, regardless of their apparently weak intracellular diffusion and the absence of synergy between these antibiotics, which has been observed during the course of experimental infections in animals (12). Indeed, the ratio between the intracellular concentration and the extracellular concentration assessed in HeLa cells is 0.6 for penicillin G and 0.12 for ampicillin (3).…”

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confidence: 99%

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Inhibition of intracellular growth of Listeria monocytogenes by antibiotics

Michelet¹,

Avril²,

Cartier³

et al. 1994

Antimicrob Agents Chemother

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We studied the activities of 15 antibiotics on the intracellular growth of Listeria monocytogenes in a HeLa cell line. After 24 h of contact with the infected cells, the antibiotics most effective against the intracellular growth of the 10 strains tested were amoxicillin, temafloxacin, and sparfloxacin, which nevertheless failed to totally eliminate the intracellular bacteria. Rifampin and co-trimoxazole had variable effects, depending on the isolates studied. The most active combinations were amoxicillin-sparfloxacin, co-trimoxazole-gentamicin, and sparfloxacin-co-trimoxazole. The results suggest the value of using a cell culture technique to study the activities of antibiotics against certain bacteria with intracellular sites of multiplication.

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Section: Resultsmentioning

confidence: 96%

mentioning

confidence: 99%

Inhibition of intracellular growth of Listeria monocytogenes by antibiotics

Michelet¹,

Avril²,

Cartier³

et al. 1994

Antimicrob Agents Chemother

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“…70,71,73 However, in vivo synergism has not been uniformly observed and retrospective clinical studies have not consistently shown better results for combined therapy of listeriosis than simple penicillin monotherapy. 3,4,70,74 In this review, 23 of 35 (65.7%) patients with listerial endocarditis treated with the combination of penicillin or ampicillin with aminoglycosides survived the infection in comparison with ten out of 14 (71.4%) treated with penicillin monotherapy. The combination of vancomicin with gentamicin was successfully used in four patients including one in the above case studies.…”

Section: Discussionmentioning

confidence: 98%

Prosthetic valve endocarditis due to Listeria monocytogenes

Guerrero

Rivas

Rábago

et al. 2004

International Journal of Infectious Diseases

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Despite problems associated with microbial persistence and relapses in other forms of human listeriosis, antimicrobial therapy alone may be a successful treatment for listerial endocarditis, including cases occurring on prosthetic valves. Valve replacement may be reserved for complicated cases with valve dehiscense, cardiac failure or myocardial abscess. Overall mortality was 35.3%, although most patients who died did so before 1985 and since then mortality has been significantly reduced to 12%.

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“…In vivo studies using intermittent administration (every 12 h) of gentamicin in L. monocytogenes-infected rodents showed that this antibiotic did not significantly decrease the bacterial load in the spleen (18), the bloodstream (20), or the brain (3). By comparison, we found that a continuous infusion of gentamicin did significantly decrease bacterial loads in the liver, brain, and spleen compared with those in untreated mice killed at the same time.…”

Section: Discussionmentioning

confidence: 99%

Listeria monocytogenes-Infected Phagocytes Can Initiate Central Nervous System Infection in Mice

2001

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Listeria monocytogenes-infected phagocytes are present in the bloodstream of experimentally infected mice, but whether they play a role in central nervous system (CNS) invasion is unclear. To test whether bacteria within infected leukocytes could establish CNS infection, experimentally infected mice were treated with gentamicin delivered by surgically implanted osmotic pumps. Bacterial inhibitory titers in serum and plasma ranged from 1:16 to 1:256, and essentially all viable bacteria in the bloodstream of treated mice were leukocyte associated. Nevertheless, CNS infection developed in gentamicin-treated animals infected intraperitoneally or by gastric lavage, suggesting that intracellular bacteria could be responsible for neuroinvasion. This was supported by data showing that 43.5% of bacteria found with blood leukocytes were intracellular and some colocalized with F-actin, indicating productive intracellular parasitism. Experiments using an L. monocytogenes strain containing a chromosomal actA-gfpuv-plcB transcriptional fusion showed that blood leukocytes were associated with intracellular and extracellularly bound green fluorescent protein-expressing (GFP ؉ ) bacteria. Treatment with gentamicin decreased the numbers of extracellularly bound GFP ؉ bacteria significantly but did not affect the numbers of intracellular GFP ؉ bacteria, suggesting that the latter were the result of intercellular spread of GFP ؉ bacteria to leukocytes. These data demonstrate that infected leukocytes and the intracellular L. monocytogenes harbored within them play key roles in neuroinvasion. Moreover, they suggest that phagocytes recruited to infected organs such as the liver or spleen are themselves parasitized by intercellular spread of L. monocytogenes and then reenter the bloodstream and contribute to the systemic dissemination of bacteria.Listeria monocytogenes is a facultative intracellular bacterium that infects the central nervous system (CNS) of humans and domesticated animals (21, 22). Most human infections result from ingestion of contaminated food and typically manifest as febrile gastroenteritis (25). Immunosuppressed hosts, however, are much more likely to develop invasive listeriosis marked by bacteremia, CNS infection, and death (24,27). Although the precise mechanism(s) used by L. monocytogenes for entering the CNS are not clear, current theory indicates that neuroinvasive bacteria in general can enter the CNS by several different routes (37). These include invasion of microvascular endothelial cells, invasion of epithelial cells of the choroid plexus, and passage of bacteria through intercellular junctions. In addition, bacteria that are capable of intracellular survival can enter the CNS via phagocyte-facilitated infection, the major steps of which are adhesion of infected phagocytes to endothelium followed by cell-to cell spread of bacteria to endothelial cells and/or migration of infected phagocytes into the CNS (10).Experimental L. monocytogenes infection of mice shows that bacteria enter the CNS following prol...

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Lack of synergism of ampicillin and gentamicin in experimental listeriosis

Cited by 28 publications

References 15 publications

Inhibition of intracellular growth of Listeria monocytogenes by antibiotics

Inhibition of intracellular growth of Listeria monocytogenes by antibiotics

Prosthetic valve endocarditis due to Listeria monocytogenes

Listeria monocytogenes-Infected Phagocytes Can Initiate Central Nervous System Infection in Mice

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