Penicillin‐G degradation products inhibit <i>in vitro</i> granulopoiesis

Neftel, Klaus; Müller, Martin; Wälti, M; Erni, Jana; Gugler, Madeleine; Arrenbrecht, Stefan

doi:10.1111/j.1365-2141.1983.tb02093.x

Cited by 30 publications

(12 citation statements)

References 3 publications

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“…Neftel et al (17) found that a stocked penicillin-G solution showed a stronger suppressive effect on CFU-GM than a freshly prepared solution, and the degree of inhibition was closely correlated with the extent of breakdown of penicillin-G as assessed by thin layer chromatography.…”

Section: Resultsmentioning

confidence: 99%

“…Neftel et al (18) reported some cases of severe neutropenia following intravenous therapy with 'aged' penicillin-G. They have suggested that penicillin-G degradation products are responsible for neutropenia (1), and neutropenia and most of the other adverse reactions after intravenous treatment with high dosages of penicillin-G will be prevented if the penicilln-G is always given in the form of fresh bolus doses (17). Few data are available about degradation and transformation products of Q-lactam anti biotics, but such products have a chance to be relevant to neutropenia, thrombocytopenia or the other side effects.…”

Section: Resultsmentioning

confidence: 99%

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Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM).

1987

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Abstract-R-Lactamantibiotics, moxalactam (LMOX), cefotaxime (CTX), flomoxef (FMOX), cefamandole (CMD), carbenicillin (CBPC) and sulbenicillin (SBPC), suppressed colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM) dose-dependently. The suppres sive potencies for both progenitors were weakest for CBPC and SBPC, moderate for LMOX and FMOX, and strongest for CMD and CTX. The stainability of glyco protein Ilb/Illa complex in the megakaryocyte colonies by the monoclonal antibody was decreased by LMOX and CTX. These data suggest that /3-lactam antibiotics directly suppress proliferation of CFU-M and CFU-GM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM).

1987

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“…Later, we indeed found that penicillin-G, some of its semi-synthetic congeners and some cephalosporins dose-dependently inhibit human in vitro granulopoiesis in a semi-solid agar system (Neftel et al, 1983;Neftel et al, 1985). Inhibition of myeloid colony formation is illustrated in Figure 1 for two penicillins and one cephalosporin.…”

Section: Human Granulop01esismentioning

confidence: 97%

Beta-lactam antibiotics inhibit human in vitro granulopoiesis and proliferation of some other cell types

et al. 1986

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“…Inclusion of histopathologic and immunofluorescent studies (33, analysis for degradation products of antibiotics (16,18), and evaluation of the salt component of antibiotic might add to the predictive value of our model. These studies are part of our planned further investigations.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitory potency of @-lactams on in vitro granulopoiesis seems to be substantially enhanced by drug degradation (16). However, the convulsant effect, like the antimicrobial effect, depends on the presence of the intact p-lactam ring (2,36).…”

Section: Discussionmentioning

confidence: 99%

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

et al. 1988

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ABSTRACT. The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity ( p < 0.001 or < 0.01) and to a lesser extent ( p < 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections. (Pediatr Res 24: 367-372,1988) Abbreviations BCC, brain cell culture CSF, cerebrospinal fluid DIC, days in culture CST, cerebral sulfate transferase reviews of case reports (1, 2). CNS toxicity is a well-described complication of intraventricular antibiotic therapy for gramnegative bacillary ventriculitis and CSF shunt infections (l,2,4-7). Animal toxicity tests bear a relatively poor predictive value for neurotoxicity in man and require the use of a high number of animals (4,5,(8)(9)(10). Therefore, back-shifting of neurotoxicity tests from the human or animal situation to a relatively simple and reproducible system in vitro was the principal aim of the present research.There are many reports presenting evidence of dose-dependent antiproliferative effects of various antibiotics on cultured eucaryotic cells. The cell types studied include human fibroblasts (1 1), bone marrow cells (12), and dissociated brain cells (1 3). As in vitro correlative of dose-related marrow suppression by chloramphenicol it was found several decades ago that this drug inhibits mitochondria1 protein synthesis not only in bacteria but also in proliferating bone marrow cells (14, 15). More recently, the inhibition of cell proliferation has most often been studied for the @-lactam antibiotics on cultured human myeloid percursor and lymphoid cells, the clinical consequences being neutropenia and impairment of cellular and humoral immune responses induced by 6-lactams (12, 16-1 8).The purpose of our investigation was to monitor the effects of antibiotics on growth and differentiation in dissociated rat BCC which might help to pred...

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Penicillin‐G degradation products inhibit in vitro granulopoiesis

Cited by 30 publications

References 3 publications

Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM).

Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM).

Beta-lactam antibiotics inhibit human in vitro granulopoiesis and proliferation of some other cell types

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

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