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Neutropenia after penicillins: Toxic or immune-mediated?

Neutropenie nach Penicillin: Toxisch oder immunvermittelt?

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Summary

Eight patients treated with a total of 220–550 million U penicillin-G developed neutropenia. These cases have been compared with eight patients receiving a similar dose of penicillin-G with no adverse reactions and with eight untreated subjects. All penicillin-treated patients showed raised levels of antipenicillin IgG antibodies and lymphocyte culture stimulation indices. These values were highest in the neutropenia group. Both of the two tests significantly descriminated the three groups. Antineutrophil antibodies could be detected in four of seven neutropenic patients with a staphylococcal-slide-assay while indirect immunofluorescence and microcytotoxicity tests failed to reveal these antibodies. The literature dealing with neutropenias induced by penicillin-G and its congeners is reviewed. We conclude that (1) penicillin-G in doses exceeding a total of 200 million U frequently induces neutropenia, (2) an immune-mediated pathogenesis is highly probable, (3) neutropenia after penicillins is different from two hither-to accepted types of this side effect, (4) sufficiently high amounts of penicillin-G intravenously always induce sensitization against this drug.

Zusammenfassung

Acht Patienten entwickelten nach total 220–550 Millionen E Penicillin-G i.v. eine Neutropenie. Wir verglichen immunologische Daten dieser Fälle mit denjenigen von acht Patienten, die mit vergleichbaren Penicillin-G-Dosen ohne ersichtliche Nebenwirkungen behandelt wurden, sowie mit denjenigen von acht unbehandelten Gesunden. Alle mit Penicillin Behandelten zeigten im Vergleich zu den Unbehandelten erhöhte Spiegel von anti-Penicillin IgG und einen stark positiven Lymphozyten-Stimulationstest mit Penicillin. Beide Untersuchungen ergaben die höchsten Werte innerhalb der Neutropeniegruppe und unterschieden alle drei Gruppen signifikant voneinander. Bei vier von sieben Neutropenikern konnten mit einem Objektträgertest unter Verwendung von Protein A enthaltenden Staphylokokken, antineutrophile Antikörper nachgewiesen werden. Mit indirekter Immunfluoreszenz und Mikrozytotoxizitätstest gelang dagegen in keinem Fall ein Antikörpernachweis. Die Literatur über Neutropenie nach Penicillin und seinen Derivaten wurde durchgesehen. Schlußfolgerungen: (1) Über 200 Mio E Penicillin-G i.v. induziert häufig eine Neutropenie, (2) ein immunvermittelter Mechanismus ist sehr wahrscheinlich, (3) die Neutropenie nach Penicillinen ist nicht identisch mit einem der zwei bisher akzeptierten Typen der medikamentös induzierten Immunneutropenie (Amidopyrin-Typ resp. Procainamid-Typ), (4) genügend hohe Dosen von Penicillin-G erzeugen immer einen positiven Lymphozyten-Stimulationstest und einen Anstieg von Penicillin-spezifischen IgG.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Berne, Berne, Switzerland

    K. A. Neftel

  2. Institute of Clinical Immunology, Berne, Switzerland

    M. Wälti, H. Spengler & A. L. de Weck

  3. Department of Internal Medicine, University of Zurich, Zurich, Switzerland

    A. von Felten

  4. Department of Medicine, Harvard Medical School, Hematology-Oncology Unit, Massachusetts General Hospital, Boston, USA

    S. A. Weitzman

  5. Medical Department, Solothurn, Switzerland

    H. Bürgi

Authors
  1. K. A. Neftel
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  2. M. Wälti
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  3. H. Spengler
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  4. A. von Felten
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  5. S. A. Weitzman
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  6. H. Bürgi
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  7. A. L. de Weck
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Neftel, K.A., Wälti, M., Spengler, H. et al. Neutropenia after penicillins: Toxic or immune-mediated?. Klin Wochenschr 59, 877–888 (1981). https://doi.org/10.1007/BF01721921

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  • DOI: https://doi.org/10.1007/BF01721921

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