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Epidemiology of extended spectrum β-lactamases

Epidemiologie der Breitspektrum-β-Laktamasen

  • Addendum II
  • New Blasmid — Borne β-Lactamases
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Summary

β-lactamases play a major part in resistance, as recently redemonstrated by the emergence of extended spectrum β-lactamases. Since its discovery in FR Germany, SHV-2 has been reported from four continents and CTX-1 (TEM-3) was established in at least 26 French hospitals. More than 12 other enzymes have been individualized. The newest aspect of resistance was probably underestimated because most strains of enterobacteria (mainlyKlebsiella pneumoniae) appeared susceptible to oxyimino-β-lactams as suggested by MICs or diameters of inhibition zone sizes. The double-disk synergy test between amoxicillin/clavulanic acid and oxyimino-β-lactams was useful to easily detect two susceptibility patterns (CTX, CAZ). Extended spectrum β-lactamases isolated among nosocomial isolates of enterobacteria (urines, blood, wound, sputum cultures) mostly from intensive care units have spread through hospitals. If outbreaks were described, numerous serotypes were identified inKlebsiella pneumoniae. In France the distribution of extended spectrum β-lactamases showed that CTX-1 (TEM-3) was well distributed among ten species unlike SHV-type enzymes (SHV-2, SHV-3, SHV-4) preferentially detected inKlebsiella pneumoniae. A majority of strains produced CAZ-type enzymes inEscherichia coli. Some isolates produced two extended spectrum β-lactamases. In Tunisia extended spectrum β-lactamase producing strains were mainly identified among pediatric isolates ofKlebsiella pneumoniae, Salmonella andEscherichia coli; SHV-2 was predominant but recently CTX-1 and two other types with an isoelectric point of 6.35 and 5.4 (phenotype CTX) were individualized. Because plasmid-encoded, this mechanism was spreading in France among enterobacteria with other resistance markers (e.g. netilmicin, amikacin) for CTX-1 unlike SHV-2. The transferability of extended spectrum β-lactamases appeared to occur less frequently from isolates of enterobacteria issued from Tunis and particularly for the first isolates ofSalmonella wien. The transmissible resistance to other antibiotics such as aminoglycosides was demonstrated in 1988. It seems highly likely that the use of newer antibiotics favors the appearance of extended spectrum β-lactamases.

Zusammenfassung

β-Laktamasen spielen in der bakteriellen Resistenz eine entscheidende Rolle; dies bestätigte sich erneut mit dem Auftreten von Breitspektrum-β-Laktamasen. Nach Erstentdeckung in der Bundesrepublik wurde SHV-2 in vier Kontinenten nachgewiesen; in mindestens 26 französischen Krankenhäusern trat CTX-1 (TEM-3) auf. Mehr als 12 weitere Enzyme wurden identifiziert. Die Bedeutung dieser neuesten Resistenz-Form wurde wahrscheinlich unterschätzt, da die meisten Stämme von Enterobakterien (vor allemKlebsiella pneumoniae nach Ergebnissen der MHK-Bestimmungen oder Hemmhofdurchmesser gegen Oxyimino-β-Laktame empfindlich zu sein schienen. Zwei Empfindlichkeitsmuster (CTX, CAZ) lassen sich mit dem Doppel-Blättchen-Synergismus-Test von Amoxicillin/Clavulansäure und Oxyimino-β-Laktamen ohne Schwierigkeiten nachweisen. In den Krankenhäusern haben sich Breitspektrum-β-Laktamasen ausgebreitet, die bei nosokomialen Enterobakterien-Stämmen (aus Urin-, Blut-, Wund- und Sputumkulturen), vorwiegend aus Intensivstationen, zu finden sind. Bei Ausbrüchen vonKlebsiella pneumoniae-Infektionen fanden sich zahlreiche Serotypen. Untersuchungen zur Verteilung der Breitspektrum-β-Laktamasen in Frankreich zeigten, daß CTX-1 (TEM-3) unter zehn Spezies verbreitet ist, während sich die Enzyme vom Typ SHV (SHV-2, SHV-3, SHV-4) vorwiegend inKlebsiella pneumoniae nachweisen lassen. BeiEscherichia coli bildeten die meisten Stämme Enzyme vom Typ CAZ. Manche Isolate bildeten zwei Breitspektrum-β-Laktamasen. Breitspektrum-β-Laktamasebildung durchKlebsiella pneumoniae, Salmonella undEscherichia coli wurde in Tunesien vor allem in Isolaten aus der Pädiatrie nachgewiesen; am häufigsten fand sich SHV-2, kürzlich wurden aber auch CTX-1 und zwei andere Typen mit isoelektrischem Punkt von 6,35 und 5,4 (Phänotyp CTX) identifiziert. Da diese Enzyme durch Plasmide kodiert sind, breitete sich dieser Resistenzmechanismus in Frankreich für CTX-1 zusammen mit anderen Resistenzmarkern aus (z. B. Resistenz gegen Netilmicin, Amikacin), was für SHV-2 nicht der Fall war. Bei Enterobakterien-Isolaten aus Tunis, vor allem den erstenSalmonella wien-Isolaten, war die Übertragbarkeit von Breitspektrum-β-Laktamasen offensichtlich seltener. 1988 wurde übertragbare Resistenz gegen andere Antibiotika wie Aminoglykoside festgestellt. Es scheint sehr unwahrscheinlich, daß die Verwendung neuerer Antibiotika das Auftreten von Breitspektrum-β-Laktamasen begünstigt.

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Authors and Affiliations

  1. Institut Pasteur, Unité d'Ecologie Bactérienne, F-75015, Paris

    A. Philippon M.u.D.

  2. CHU Cochin-Port Royal, Laboratoire de Bactériologie, F-75014, Paris

    A. Philippon M.u.D.

  3. Hôpital Charles Nicolle, Service de Bactériologie-Virologie, Tunis, Tunisia

    S. Ben Redjeb M.D. & A. Ben Hassen M.D.

  4. technician, CHU Cochin-Port Royal, Laboratoire de Bactériologie, F-75014, Paris, France

    G. Fournier

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  1. A. Philippon M.u.D.
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  3. A. Ben Hassen M.D.
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Additional information

This study was supported in part by a grant to A. P. (N° 87-33403E) from the Caisse Nationale de l'Assurance Maladie des Travailleurs Salariés.

supported by Pfizer GmbH, Karlsruhe

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Philippon, A., Ben Redjeb, S., Ben Hassen, A. et al. Epidemiology of extended spectrum β-lactamases. Infection 17, 347–354 (1989). https://doi.org/10.1007/BF01650727

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