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The antimicrobial activity of cefotaxime: Comparative multinational hospital isolate surveys covering 15 years

Antimikrobielle Aktivität von Cefotaxim: Vergleich multinationaler Erregerstatistiken von Krankenhaus-Isolaten über 15 Jahre

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Summary

The “third-generation” cephalosporins (3GC) have emerged as one of the most significant therapeutic entities in the last 15 years. These 3GC compounds (using cefotaxime as a model) have generally maintained their potency and spectrum of activity against important pathogens. However, the continuing popularity of this class associated with local, regional, or national-level use or abuse has led to efficacy reduction against some organism populations associated with selection of Class I cephalosporinase, stably derepressed mutants predominantly amongCitrobacter andEnterobacter spp.; emergence of extended-spectrum β-lactamase producingEnterobacteriaceae (usuallyKlebsiella spp.), as well as some isolates mimicking Class I-type resistance patterns; and lastly, altered PBP-mediated resistance among pneumococci,Haemophilus influenzae and pathogenicNeisseria spp. Some of these resistance patterns had been present prior to the clinical introduction of 3GCs and have only significantly threatened their use in the last 5 years. Prudent application of these 3GC drugs should be the goal for this decade as follows: 1) use as monotherapy at appropriate doses and frequencies only for organisms with low potential for mutational events; 2) use combination therapy routinely for organisms such asCitrobacter, Enterobacter, some indole-positive proteae andPseudomonas aeruginosa, to minimize emerging resistance clones; 3) use conservatively in high risk patients to minimize “super-colonization” by emerging problem bacteria (e.g. vancomycin-resistant enterococci,Xanthomonas maltophilia etc.); 4) use only those agents among 3GCs that have documented safety, broad clinical applications to all age groups, acceptable pharmacokinetic features and clear cost-saving potential; and 5) use in prophylaxis (surgical procedure, selective decontamination), should be focused toward single-dose or short-course regimens to reduce total hospital-wide exposure to broad-spectrum β-lactam drugs. If these recommendations are followed and coupled with good infection control/epidemiology practices, the 3GC drugs will continue to have an important role in the chemotherapy of moderate-to-severe infections in this decade. However, physicians will need to be more knowledgeable about alternative treatment regimens when the described resistances appear in the hospital environments or in the individual patient.

Zusammenfassung

Die Cephalosporine der dritten Generation (3GC) stellen eine der bedeutendsten therapeutischen Entwicklungen der letzten 15 Jahre dar. Die Aktivität und das Wirkungsspektrum der 3GC Substanzen (mit Cefotaxim als Modell) gegen wichtige Erreger sind weitgehend erhalten geblieben. Der lokale, regionale oder nationale Gebrauch oder Mißbrauch dieser beliebten Substanzen ist jedoch mit einem Aktivitätsverlust gegen einige Erregergruppen verbunden. Er geht einher mit der Selektion stabil dereprimierter Mutanten mit Produktion von Cephalosporinasen oder Klasse-I beiCitrobacter- undEnterobacter-Spezies; Verbreitung vonEnterobacteriaceae, die β-Laktamasen mit erweitertem Breitspektrum produzieren (meistKlebsiella spp.) sowie einiger Isolate, die Klasse-I Resistenzmuster nachahmen; und schließlich PBP-assoziierte Resistenz bei Pneumokokken,Haemophilus influenzae, undNeisseria spp. Manche dieser Resistenzmuster waren schon vor Einführung der 3GC in die Klinik vorhanden, haben aber deren Wirksamkeit erst in den letzten 5 Jahren bedroht. Sorgsamer Gebrauch der 3GC sollte das Ziel für dieses Jahrzehnt sein. 1. Die Anwendung in Monotherapie sollte in adäquaten Dosen und Dosierungsintervallen erfolgen und nur bei Erregern, die ein niedriges Mutationspotential haben. 2. Für Erreger wieCitrobacter, Enterobacter, einige indolpositiv Proteus-Arten undPseudomonas aeruginosa sollte eine Kombinationstherapie routinemäßig eingesetzt werden, um das Auftreten resistenter Klone auf ein Minimum zu reduzieren. 3. Zurückhaltende Anwendung bei Hochrisikopatienten, um die Überwucherung durch Bakterien wie Vancomycin-resistente Enterokokken,Xanthomonas maltophilia und andere zu vermeiden. 4. Unter den 3GC sollten nur diejenigen Substanzen mit bewiesener Sicherheit, breiter klinischer Anwendbarkeit in allen Altersgruppen, akzeptablen pharmakokinetischen Eigenschaften und eindeutigem Potential zur Kosteneinsparung verwendet werden. 5. Bei prophylaktischer Anwendung (chirurgische Eingriffe, selektive Dekontamination) sollte mit Einzeldosis oder Kurzzeit-Schemata erfolgen, um im Krankenhausbereich die Anwendung von Breitspektrum-Antibiotika in Grenzen zu halten. Bei Befolgung dieser Empfehlungen und Anwendung guter Infektions-Kontroll-Programme werden die 3GC in diesem Jahrzehnt ihre bedeutende Rolle in der Chemotherapie mäßiggradiger bis schwerer Infektionen behalten. Die Ärzte müssen sich aber mehr Wissen über alternative Behandlungsmöglichkeiten aneignen, da die beschriebenen Resistenzen in der Krankenhausumgebung und beim einzelnen Patienten auftreten können.

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Jones, R.N. The antimicrobial activity of cefotaxime: Comparative multinational hospital isolate surveys covering 15 years. Infection 22 (Suppl 3), S152–S160 (1994). https://doi.org/10.1007/BF01782700

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