Supported by an educational grant from Bayer AG, Germany

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1 Supported by an educational grant from Bayer AG, Germany

2 c. Garrard (Ed.) Ciprofloxacin i. v. Defining Its Role in Serious Infections International Symposium, Salzburg, September 1993 Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest

3 DR. CHRISTOPHER GARRARD John Radcliffe Hospital Intensive Care Director Oxford OX3 9 DU, United Kingdom ISBN-13: DOl: / e-isbn -13: This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concemed, specifically the rights of translation, reprintmg, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this pubhcation or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. Spnnger-Verlag Berlin Heidelberg 1994 Softcover reprint of the hardcover I st edition 1994 The use of registered names, trademarks, etc in this publication does not imply, even i~ the absence of a specific statement, that such names are exempt from the relevant protective laws and regulation and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting: Storch GmbH, Wiesentheid 23/ I 0 - Printed on acid-free paper

4 Preface The fluoroquinolone ciprofloxacin has been used in a wide range of bacterial infections. This antibacterial agent has a broad spectrum of activity and is associated with relatively few side effects. Both oral and intravenous administration can achieve effective levels at the focus of infection. In addition to demonstrable efficacy against a wide range of micro-organisms, ciprofloxacin is endowed with other pharmacodynamic characteristics. Because of its favourable pharmacokinetics and pharmacodynamics ciprofloxacin proved to be efficacious following oral doses ranging from 250 to 750 mg bid or i.v. doses of mg bid against "less severe" infections. However, infections in immunocompromised patients and other severe infections might necessitate i.v. doses of 400 mg bid-tid. A symposium was held in Salzburg, Austria in September 1993 to address the issue of efficacy and safety of ciprofloxacin 400 mg i. v. in the treatment of severe infections. In addition, in vitro data and results generated in experimental animals were presented, demonstrating new pharmacodynamic characteristics of ciprofloxacin, probably contributing to its clinical efficacy: It is tempting to speculate that effects such as bactericidal efficacy against extremely slowly growing bacteria, pronounced postantibiotic effect and endotoxin binding capacity might be of clinical relevance. In clinical studies it could be demonstraed that, provided ciprofloxacin was dosed adequately, bacteria were eradicated in the majority of patients with severe pneumonia within one day. A recent, clinically controlled study has confirmed that the efficacy of 400 mg ciprofloxacin tid is comparable to that of imipenemlcilastin in the treatment of severe nosocomial pneumonia. Similarly, ciprofloxacin is an effective and safe drug for use in the immunocompromised host or neutropenic patient even if a total daily dose of 600 and 900 mg combined with an aminoglycoside is used as empiric therapy. Combination with other antibiotics such as the semisynthetic penicillins (e.g. piperacillin) not only reduces the rate of development of resistance but may enhance efficacy against organisms such as Pseudomonas aeruginosa. The safety of ciprofloxacin has been established over the past decade of clinical use in inpatients and large populations of outpatients. Adverse drug reactions (ADR) at the higher doses of 400 mg twice or three times daily are comparable to or lower than those observed for control drugs, and there appears to be no dose-related dependency of ADR.

5 Intravenous ciprofloxacin in doses of 400 mg twice or three times daily provides effective eradication of a wide range of organisms, including those with marginal MIC values. Combined with a safety profile comparable or better than controls, intravenous ciprofloxacin provides effective therapy for the treatment of a wide range of patients with severe infection. Oxford, August 1994 Christopher S. Garrard

6 Contents Effect of Quinolones Against Slowly Growing Bacteria A. DALHOFF, S. MATUTAT, and U. ULLMANN... 1 The Postantibiotic Effect of Ciprofloxacin B. WIEDEMANN and B. KRATZ The Effects of Different Types of Antimicrobial Agents on Plasma Endotoxin Activity in Gram-Negative Bacterial Infection D. NITSCHE, C. SCHULZE, S. OESSER, A. DALHOFF, and M. SACK Dose-Finding Investigations of Intravenous Ciprofloxacin in a Pharmacodynamic Model A. BAUERNFEIND and S. KLJUCAR The Relationship Between Ciprofloxacin Blood Concentrations, MIC Values, Bacterial Eradication, and Clinical Outcome in Patients with Nosocomial Pneumonia J. J. SCHENTAG Efficacy and Safety of Ciprofloxacin in Various Intravenous Dosages S. KLJUCAR, M. HEIMESAAT, A. BAUERNFEIND, E. VON PRITzBUER, and J. TIMM Intravenous Ciprofloxacin Versus ImipenemlCiiastatin in the Treatment of Severe Pneumonia K. V. LEEPER Conversion of Intravenous to Oral Ciprofloxacin: Observing the "Like-to-Like" Phenomenon C. H. NIGHTINGALE, P. P. BELLIVEAU and R. QUINTILIANI Therapeutic Use of Quinolones in Oncology G. MASCHMEYER

7 Ciprofloxacin in Neutropenic Host Infection H. GIAMARELLOU Intravenous Ciprofloxacin for the Treatment of Lower Respiratory Tract Infections: Preliminary Results P. MANGIAROTTI and C. GRASSI Integrated Safety Profile of Intravenous Ciprofloxacin C. REITER, M. PFEIFFER, R. HULLMANN, and P. SCHACHT

8 List of Contributors A. BAUERNFEIND Max von Pettenkofer Institute of Hygiene and Medical Microbiology PettenkoferstraBe 9a Munich, Germany P. P. BELLIVEAU Department of Pharmacy University of Massachusetts Medical Center 55 Lake Avenue North Worcester, MA 06115, USA A. DALHOFF Institut fur Medizinische Mikrobiologie und Virologie Christian-Albrechts-Universitat Brunswiker StraBe Kiel, Germany H. GIAMARELLOU Infectious Diseases Section First Department of Propedeutic Medicine Athens University School of Medicine Laiko General Hospital Athens, Greece C. GRASSI Institute of Respiratory Diseases University of Pavia via Taramelli Pavia, Italy M. HEIMESAAT Department of Anesthesiology and Intensive Care Medicine Deutsches Rotes Kreuz Kliniken Westend Spandauer Damm Berlin, Germany R. HULLMAN M + I Services International Pharma Forschungszentrum Bayer AG Postfach Wuppertal, Germany

9 S.KuUCAR Department of Anesthesiology and Intensive Care Medicine Deutsches Rotes Kreuz Kliniken Westend Spandauer Damm Berlin, Germany K. V. LEEPER Division of Pulmonary and Critical Care Medicine University of Tennessee 956 Court A venue Memphis, TN 38163, USA P. MANGIAROTTI Institute of Respiratory Diseases University of Pavia via Taramelli Pavia, Italy G. MASCHMEYER Universitatsklinikum Rudolf Virchow Robert -R6ss1e-Klinik Lindenbergerweg Berlin, Germany S.MATUTAT Institut fur Medizinische Mikrobiologie und Virologie Christian-Albrechts-Universitat Brunswiker StraBe Kiel, Germany C. H. NIGHTINGALE Office for Research Hartford Hospital 80 Seymour Street Hartford, CT , USA D. NITSCHE Surgical Research Christian-Albrechts-U ni versitat Michaelis-Str Kiel, Germany S.OESSER Surgical Research Christian-Albrechts-U ni versiat Michaelis-Str Kiel, Germany

10 M. PFEIFFER Institute of Drug Safety International Pharma Forschungszentrum Bayer AG Postfach Wuppertal, Germany R. QUINTILIANI Division of Infectious Diseases and Allergy-Immunology Hartford Hospital 80 Seymour Street Hartford, CT , USA C. REITER Institute of Drug Safety International Pharma Forschungszentrum Bayer AG Postfach Wuppertal, Germany M. SACK Surgical Research Christian-Albrechts-U ni versitat Michaelis-Str Kiel, Germany P. SCHACHT Clinical Project Management International Pharma Forschungszentrum Bayer AG Postfach Wuppertal, Germany 1. J. SCHENTAG School of Pharmacy State University of New York at Buffalo Clinical Pharmacokinetics Laboratory Millard Fillmore Hospital 3 Gates Circle Buffalo, NY 14209, USA C. SCHULZE Surgical Research Christian-Albrechts-Universitat Michaelis-Str Kiel, Germany

11 J. TIMM Scientific Statistics Unit Fachbereich 3 Mathematik Universitat Bremen BibliothekstraBe Bremen, Germany U. ULLMANN Institut fur Medizinische Mikrobiologie und Virologie Christian-Albrechts-U niversitlit Brunswiker StraBe lO3 Kiel, Germany E. VON PRmBUER Bremen State Institute of Hygiene St. liirgen-strabe Bremen, Germany