Background: It has become an article of faith that appropriate antibiotic therapy is needed for best outcomes during a serious infection. Despite this long-held view, there is some debate about the role of appropriate outcome in serious infections, in particular with nosocomial pneumonia. Therefore, more recent data on adequacy of antibiotic therapy and outcomes were reviewed. Methods: The medical literature from 1997 to 2004 was surveyed for articles that directly dealt with appropriate therapy. Search terms included ‘appropriate and inappropriate antibiotic therapy’, ‘adequate antibiotic therapy’, ‘resistance and antibiotic failures’ and ‘delayed therapy’. The data were abstracted to obtain their essential findings. Results: In bacteremia, data are most persuasive that appropriate and timely therapy significantly influences outcomes. Areas where this may not be the case are studies where coagulase-negative staphylococci are isolated in large numbers or in studies where the incidence of appropriate therapy is high. One area where data are not conclusive concerns the treatment of enteric bacteria carrying extended spectrum betalactamases, where the only cephalosporin of concern is ceftazidime. There is not enough data to compare carbapenems with specific cephalosporins to conclude that these are the most appropriate agents. The studies in regard to nosocomial pneumonias are not as conclusive as those with bacteremias. There appears to be a subset of patients that do not respond to therapy or do not survive, which confounds studies of this population; however, most studies favor a role of appropriate therapy. Conclusions: Appropriate antibiotic therapy has several dimensions. It improves outcomes in most serious diseases. Timing of administration and appropriateness, based on susceptibility, are the most important determinants, but dosing intervals and dose probably play similarly important roles in outcomes that have not been examined exhaustively in humans. Other aspects of appropriate therapy that deserve attention include a shift to more ‘resistance’-proof antibiotics in empiric therapy, which may be accompanied by better outcomes.

1.
Andes D, Craig WA: Animal model pharmacokinetics and pharmacodynamics: A critical review. Int J Antimicrob Agents 2002;19:261–268.
2.
Harbarth S, Garbino J, Pugin J, et al: Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 2003;115:529–535.
3.
Leibovici L, Paul M, Poznanski O, et al: Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: A prospective, observational study. Antimicrob Agents Chemother 1997;41:1127–1133.
4.
Behrendt G, Schneider S, Brodt HR, et al: Influence of antimicrobial treatment on mortality in septicemia. J Chemother 1999;11:179–186.
5.
Kollef MH, Sherman G, Ward S, Fraser VJ: Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients. Chest 1999;115:462–474.
6.
Ibrahim EH, Sherman G, Ward S, et al: The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000;118:146–155.
7.
Blot S, Vandewoude K, De Bacquer D, Colardyn F: Nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in critically ill patients: Clinical outcome and length of hospitalization. Clin Infect Dis 2002;34:1600–1606.
8.
Iregui M, Ward S, Sherman G, et al: Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002;22:262–268.
9.
Dupont H, Montravers P, Gauzit R, Veber B, Pouriat JL, Martin C, Club d’Infectiologie en Anesthesie-Reanimation: Outcome of postoperative pneumonia in the Eole study. Intensive Care Med 2003;29:179–188.
10.
Valles J, Rello J, Ochagavia A, et al: Community-acquired bloodstream infection in critically ill adult patients: Impact of shock and inappropriate antibiotic therapy on survival. Chest 2003;123:1615–1624.
11.
Zaragoza R, Artero A, Camarena JJ, et al: The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit. Clin Microbiol Infect 2003;9:412–418.
12.
MacArthur RD, Miller M, Albertson T, et al: Adequacy of early empiric antibiotic treatment and survival in severe sepsis: Experience from the MONARCS trial. Clin Infect Dis 2004;38:284–288.
13.
Clec’h C, Timsit JF, De Lassence A, et al: Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: Influence of disease severity. Intensive Care Med 2004;30:1327–1333.
14.
Heyland DK, Cook DJ, Griffith L, et al: The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group. Am J Respir Crit Care Med 1999;59:1249–1256.
15.
Thylefors JD, Harbarth S, Pittet D: Increasing bacteremia due to coagulase-negative staphylococci: Fiction or reality. Infect Control Hosp Epidemiol 1998;8:581–589.
16.
Pelz RK, Lipsett PA, Swoboda SM, et al: Vancomycin-sensitive and vancomycin-resistant enterococcal infections in the ICU: Attributable costs and outcomes. Intensive Care Med 2002;28:692–697.
17.
Kang CI, Kim SH, Kim HB, et al: Pseudomonas aeruginosa bacteremia: Risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Clin Infect Dis 2003;37:745–751.
18.
Lodise TP, McKinnon PS, Swiderski L, Rybak MJ: Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis 2003;36:1418–1423.
19.
Wong-Beringer A, Hindler J, Loeloff M, et al: Molecular correlation for the treatment outcomes in bloodstream infections caused by Escherichia coli and Klebsiella pneumoniae with reduced susceptibility to ceftazidime. Clin Infect Dis 2002;34:135–146.
20.
Kim YK, Pai H, Lee HJ, et al: Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: Epidemiology and clinical outcome. Antimicrob Agents Chemother 2002;46:1481–1491.
21.
Du B, Long Y, Liu H, et al: Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: Risk factors and clinical outcome. Intensive Care Med 2002;28:1718–1723.
22.
Paterson DL, Ko WC, Von Gottberg A, et al: Antibiotic therapy for Klebsiella pneumoniae bacteremia: Implications of production of extended-spectrum beta-lactamases. Clin Infect Dis 2004;39:31–37.
23.
Houck PM, Bratzler DW, Nsa W, et al: Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 2004;164:637–644.
24.
Jaccard C, Troillet N, Harbarth S, et al: Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis. Antimicrob Agents Chemother 1998;42:2966–2977.
25.
Carmeli Y, Troillet N, Eliopoulos GM, Samore MH: Emergence of antibiotic-resistant Pseudomonas aeruginosa: Comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999;43:1379–1382.
26.
Fink MP, Snydman DR, Niederman MS, et al: Treatment of severe pneumonia in hospitalized patients: Results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother 1994;38:547–557.
27.
Pechere JC, Vladoianu IR: Development of resistance during ceftazidime and cefepime therapy in a murine peritonitis model. J Antimicrob Chemother 1992;29:563–573.
28.
Chow JW, Fine MJ, Shlaes DM, et al: Enterobacter bacteremia: Clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med 1991;115:585–590.
29.
Schwaber MJ, Graham CS, Sands BE, et al: Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species. Antimicrob Agents Chemother 2003;47:1882–1886.
30.
Kollef MH, Ward S, Sherman G, et al: Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices. Crit Care Med 2000;28:3456–3464.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.