Review Article| Volume 90, ISSUE 6, P1265-1277, November 2006

Download started.


Clinical Approach to Antibiotic Failure

      Sometimes antibiotics fail or appear to fail, and the clinician must determine the reasons for a suboptimal response. However, before concluding that an antibiotic has failed, it is important to remember that, even when antibiotics have their desired effect, the patient's response may not be immediate. Most immunocompetent patients will show some clinical response to appropriate antibiotic therapy within 24 to 48 hours, although various objective parameters of the infectious process may lag behind the overall clinical response. For example, patients with Rocky Mountain spotted fever often feel better within 24 to 48 hours, but their fever may not begin to respond for an additional 2 to 3 days. Similarly, patients with pneumonia frequently experience a diminution in fever and toxicity in the first few days after institution of antibiotics, but the chest radiograph does not immediately reflect the patient's improvement and may actually appear to worsen before it ultimately improves. A similar observation describes cerebrospinal fluid during therapy for bacterial meningitis, which may temporarily worsen (ie, manifest a greater leukocytosis) even as the patient improves. Some classic parameters of infection are atypical on presentation. For example, patients with severe infection may develop leukopenia instead of leukocytosis, while others present with hypothermia instead of fever. Such patients will “respond” to treatment of their infection by an actual rise in white blood cell count or temperature.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Medical Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Cunha B.A. Infectious diseases in critical care medicine. Marcel Dekker, New York1998
        • Falagas M.E.
        • Vergidis P.I.
        Narrative review: diseases that masquerade as infectious cellulitis.
        Ann Intern Med. 2005; 142: 47-55
        • Donlan R.M.
        Biofilm formation: a clinically relevant microbiological process.
        Clin Infect Dis. 2001; 33: 1387-1392
        • Pankey G.A.
        • Sabath L.D.
        Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections.
        CID. 2004; 38: 864-870
        • Lewis II, J.S.
        • Jorgensen J.H.
        Inducible clindamycin resistance in staphylococci: should clinicians and microbiologists be concerned?.
        CID. 2005; 40: 280-285
        • Perlman D.C.
        • Segal Y.
        • Rosenkranz S.
        • et al.
        The clinical pharmacokinetics of rifampin and etahmbutol in HIV-infected persons with tuberculosis.
        CID. 2005; 41: 1638-1647
        • Tappero J.W.
        • Bradford W.Z.
        • Agerton T.B.
        • et al.
        Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana.
        CID. 2005; 41: 461-469
        • Hessen T.H.
        • Kaye D.
        Principles of use of antibacterial agents.
        Infect Dis Clin N Am. 2004; 18: 435-450
        • Tunkel A.R.
        Acute meningitis.
        in: Mandell G.L. Bennett J.E. Dolin R. Principles and practice of infectious disease. 6th edition. Elsevier, Philadelphia2005
        • Silverman J.A.
        • Mortin L.I.
        • Vanpraagh A.D.
        • et al.
        Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact.
        J Infect Dis. 2005; 191: 2149-2152
        • Schmidt-Ioanas M.
        • de Roux A.
        • Lode H.
        New antibiotics for the treatment of severe staphylococcal infection in the critically ill patient.
        Curr Opin Crit Care. 2005; 11: 481-486
        • Levison M.E.
        Pharmacodynamics of antimicrobial drugs.
        Infect Dis Clin N Am. 2004; 18: 451-465
        • Schentag J.J.
        • Gilliland K.K.
        • Paladino J.A.
        What have we learned from pharmacokinetic and pharmacodynamic theories?.
        CID. 2001; 32: S39-S46
        • Craig W.A.
        Does the dose matter?.
        CID. 2001; 33: S233-S237
        • Craig W.A.
        Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men.
        CID. 1998; 26: 1-12
        • Liu P.
        • Derendorf H.
        Antimicrobial tissue concentrations.
        Infect Dis Clin N Am. 2003; 17: 599-613
        • Barza M.
        Pharmacologic principles.
        in: Gorbach S.L. Bartlett J.G. Blacklow N.R. Infectious diseases. 3rd edition. Lippincott Williams & Williams, Philadelphia2004