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General Principles of Antimicrobial Therapy

      Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.
      AST ( antimicrobial susceptibility testing), CSF ( cerebrospinal fluid), ESBL ( extended-spectrum β-lactamase), G6PD ( glucose-6-phosphate dehydrogenase), HIV ( human immunodeficiency virus), MIC ( minimum inhibitory concentration), MRSA ( methicillin-resistant Staphylococcus aureus), OPAT ( outpatient parenteral antimicrobial therapy), UTI ( urinary tract infection)
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        • ISDA, Infectious Diseases Society of America Web site
        Standards, practice guidelines, and statements developed and/or endorsed by IDSA.
        (Accessed December 16, 2010.)
        • Mandell LA
        • Wunderink RG
        • Anzueto A
        • et al.
        Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
        Clin Infect Dis. 2007; 44: S27-S72
        • Ibrahim EH
        • Sherman G
        • Ward S
        • Fraser VJ
        • Kollef MH
        The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.
        Chest. 2000; 118: 146-155
        • 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
        • Tunkel AR
        • Hartman BJ
        • Kaplan SL
        • et al.
        Practice guidelines for the management of bacterial meningitis.
        Clin Infect Dis. 2004; 39: 1267-1284
        • Thompson RL
        • Wright AJ
        General principles of antimicrobial therapy.
        Mayo Clin Proc. 1998; 73: 995-1006
        • Clinical and Laboratory Standards Institute
        (Web site Accessed December 16, 2010.)
        • Pillai SK
        • Eliopoulos GM
        • Moellering Jr, RC
        Section E: anti-infective therapy: principles of anti-infective therapy.
        in: Mandell GL Bennett JE Dolin R 7th ed. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Vol 1. Churchill Livingstone/Elsevier, Philadelphia, PA2010
        • Drusano GL
        Human pharmacodynamics of beta-lactams, aminoglycosides and their combination.
        Scand J Infect Dis Suppl. 1990; 74: 235-248
        • Baddour LM
        • Wilson WR
        • Bayer AS
        • et al.
        Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association.
        Circulation. 2005; 111: e394-e434
        • Levison ME
        Pharmacodynamics of antimicrobial drugs.
        Infect Dis Clin North Am. 2004; 18 (vii.): 451-465
      1. Micromedex Healthcare Series [Internet database]. Updated periodically ed. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc.
        (Accessed December 16, 2010.)
      2. Gilbert DN Moellering Jr, RC Eliopoulos GM Chambers HF Saag MS The Sanford Guide to Antimicrobial Therapy 2010. 40th ed. Antimicrobial Therapy, Inc, Sperryville, VA2010
        • Saag M
        • Balu R
        • Phillips E
        • et al.
        High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients.
        Clin Infect Dis. 2008; 46: 1111-1118
        • Crider KS
        • Cleves MA
        • Reefhuis J
        • Berry RJ
        • Hobbs CA
        • Hu DJ
        Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.
        Arch Pediatr Adolesc Med. 2009; 163: 978-985
        • Czock D
        • Rasche FM
        Dose adjustment of ciprofloxacin in renal failure: reduce the dose or prolong the administration interval?.
        Eur J Med Res. 2005; 10: 145-148
        • Wagenlehner FM
        • Naber KG
        Fluoroquinolone antimicrobial agents in the treatment of prostatitis and recurrent urinary tract infections in men.
        Curr Infect Dis Rep. 2005; 7: 9-16
        • Silverman JA
        • Mortin LI
        • Vanpraagh AD
        • Li T
        • Alder J
        Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact.
        J Infect Dis. 2005; 191: 2149-2152
        • Tice AD
        • Rehm SJ
        • Dalovisio JR
        • et al.
        Practice guidelines for outpatient parenteral antimicrobial therapy.
        Clin Infect Dis. 2004; 38: 1651-1672
        • Begg EJ
        • Barclay ML
        • Kirkpatrick CM
        The therapeutic monitoring of antimicrobial agents.
        Br J Clin Pharmacol. 2001; 52: 35S-43S
        • Barclay ML
        • Begg EJ
        Aminoglycoside toxicity and relation to dose regimen.
        Adverse Drug React Toxicol Rev. 1994; 13: 207-234
        • Howden BP
        • Ward PB
        • Charles PG
        • et al.
        Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility.
        Clin Infect Dis. 2004; 38: 521-528
        • Rybak M
        • Lomaestro B
        • Rotschafer JC
        • et al.
        Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.
        Am J Health Syst Pharm. 2009; 66: 82-98
        • Pascual A
        • Calandra T
        • Bolay S
        • Buclin T
        • Bille J
        • Marchetti O
        Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes.
        Clin Infect Dis. 2008; 46: 201-211
        • Milo G
        • Katchman EA
        • Paul M
        • Christiaens T
        • Baerheim A
        • Leibovici L
        Duration of antibacterial treatment for uncomplicated urinary tract infection in women.
        Cochrane Database Syst Rev. 2005; (CD004682.)
        • Dunbar LM
        • Wunderink RG
        • Habib MP
        • et al.
        High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm.
        Clin Infect Dis. 2003; 37: 752-760
        • Chastre J
        • Wolff M
        • Fagon JY
        • et al.
        Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.
        JAMA. 2003; 290: 2588-2598
        • Bruns AH
        • Oosterheert JJ
        • El Moussaoui R
        • Opmeer BC
        • Hoepelman AI
        • Prins JM
        Pneumonia recovery: discrepancies in perspectives of the radiologist, physician and patient.
        J Gen Intern Med. 2010; 25: 203-206
        • Bennett JW
        • Murray CK
        • Holmes RL
        • Patterson JE
        • Jorgensen JH
        Diminished vancomycin and daptomycin susceptibility during prolonged bacteremia with methicillin-resistant Staphylococcus aureus.
        Diagn Microbiol Infect Dis. 2008; 60: 437-440
        • Shehab N
        • Patel PR
        • Srinivasan A
        • Budnitz DS
        Emergency department visits for antibiotic-associated adverse events.
        Clin Infect Dis. 2008; 47: 735-743
        • Salkind AR
        • Cuddy PG
        • Foxworth JW
        Is this patient allergic to penicillin? an evidence-based analysis of the likelihood of penicillin allergy.
        JAMA. 2001; 285: 2498-2505
        • del Real GA
        • Rose ME
        • Ramirez-Atamoros MT
        • et al.
        Penicillin skin testing in patients with a history of beta-lactam allergy.
        Ann Allergy Asthma Immunol. 2007; 98: 355-359
        • Harris AD
        • Sauberman L
        • Kabbash L
        • Greineder DK
        • Samore MH
        Penicillin skin testing: a way to optimize antibiotic utilization.
        Am J Med. 1999; 107: 166-168
        • Raja AS
        • Lindsell CJ
        • Bernstein JA
        • Codispoti CD
        • Moellman JJ
        The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency department setting.
        Ann Emerg Med. 2009; 54: 72-77
        • Costerton JW
        • Lewandowski Z
        • DeBeer D
        • Caldwell D
        • Korber D
        • James G
        Biofilms, the customized microniche.
        J Bacteriol. 1994; 176: 2137-2142
        • Anderl JN
        • Franklin MJ
        • Stewart PS
        Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin.
        Antimicrob Agents Chemother. 2000; 44: 1818-1824
        • Lynch AS
        • Robertson GT
        Bacterial and fungal biofilm infections.
        Annu Rev Med. 2008; 59: 415-428
        • Zheng Z
        • Stewart PS
        Penetration of rifampin through Staphylococcus epidermidis biofilms.
        Antimicrob Agents Chemother. 2002; 46: 900-903
        • Singh R
        • Ray P
        • Das A
        • Sharma M
        Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms.
        J Antimicrob Chemother. 2010; 65: 1955-1958
        • Zimmerli W
        • Widmer AF
        • Blatter M
        • Frei R
        • Ochsner PE
        • Foreign-Body Infection (FBI) Study Group
        Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial.
        JAMA. 1998; 279: 1537-1541
        • Bratzler DW
        • Houck PM
        Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project.
        Clin Infect Dis. 2004; 38: 1706-1715
        • Buskin SE
        • Newcomer LM
        • Koutsky LA
        • Hooton TM
        • Spach DH
        • Hopkins SG
        Effect of trimethoprim-sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis on bacterial illness, Pneumocystis carinii pneumonia, and death in persons with AIDS.
        J Acquir Immune Defic Syndr Hum Retrovirol. 1999; 20: 201-206
        • Wilson W
        • Taubert KA
        • Gewitz M
        • et al.
        Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group.
        Circulation. 2007; 116: 1736-1754
        • Fleisher GR
        The management of bite wounds.
        N Engl J Med. 1999; 340: 138-140
      3. Antibiotic prophylaxis for penetrating brain injury.
        J Trauma. 2001; 51: S34-S40
        • van de Beek D
        • de Gans J
        • McIntyre P
        • Prasad K
        Steroids in adults with acute bacterial meningitis: a systematic review.
        Lancet Infect Dis. 2004; 4: 139-143
        • Thwaites GE
        • Nguyen DB
        • Nguyen HD
        • et al.
        Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.
        N Engl J Med. 2004; 351: 1741-1751
        • Gagnon S
        • Boota AM
        • Fischl MA
        • Baier H
        • Kirksey OW
        • La Voie L
        Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a double-blind, placebo-controlled trial.
        N Engl J Med. 1990; 323: 1444-1450
        • Kaul R
        • McGeer A
        • Norrby-Teglund A
        • The Canadian Streptococcal Study Group
        • et al.
        Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome—a comparative observational study.
        Clin Infect Dis. 1999; 28: 800-807
        • McFarland LV
        Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections.
        Anaerobe. 2009; 15: 274-280
        • Amodio-Groton M
        • Madu A
        • Madu CN
        • et al.
        Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia: a pharmacoeconomic analysis.
        Ann Pharmacother. 1996; 30: 596-602
        • McCollum M
        • Rhew DC
        • Parodi S
        Cost analysis of switching from i.v. vancomycin to p.o. linezolid for the management of methicillin-resistant Staphylococcus species.
        Clin Ther. 2003; 25: 3173-3189
        • McCollum M
        • Sorensen SV
        • Liu LZ
        A comparison of costs and hospital length of stay associated with intravenous/oral linezolid or intravenous vancomycin treatment of complicated skin and soft-tissue infections caused by suspected or confirmed methicillin-resistant Staphylococcus aureus in elderly US patients.
        Clin Ther. 2007; 29: 469-477
        • Dellit TH
        • Owens RC
        • McGowan Jr, JE
        • et al.
        Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship.
        Clin Infect Dis. 2007; 44: 159-177
        • Levine OS
        • Farley M
        • Harrison LH
        • Lefkowitz L
        • McGeer A
        • Schwartz B
        Risk factors for invasive pneumococcal disease in children: a population-based case-control study in North America.
        Pediatrics. 1999; 103: E28
        • McCaig LF
        • Hughes JM
        Trends in antimicrobial drug prescribing among office-based physicians in the United States.
        JAMA. 1995; 273: 214-219
        • Gonzales R
        • Malone DC
        • Maselli JH
        • Sande MA
        Excessive antibiotic use for acute respiratory infections in the United States.
        Clin Infect Dis. 2001; 33: 757-762
        • Pepin J
        • Saheb N
        • Coulombe MA
        • et al.
        Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.
        Clin Infect Dis. 2005; 41: 1254-1260
        • Johnson L
        • Sabel A
        • Burman WJ
        • et al.
        Emergence of fluoroquinolone resistance in outpatient urinary Escherichia coli isolates.
        Am J Med. 2008; 121: 876-884

      Linked Article

      • Introduction to the Symposium on Antimicrobial Therapy
        Mayo Clinic ProceedingsVol. 86Issue 2
        • In Brief
          In this issue of Mayo Clinic Proceedings, journal readers will discover the first of 15 articles that constitute the new Symposium on Antimicrobial Therapy.1 The articles will be published sequentially in the monthly issues of the journal, ending in mid-2012. This new symposium is published in part because of readers' requests to once again address antimicrobial drugs, as was done in the Proceedings' Symposium on Antimicrobial Agents, published between October 1998 and February 2000. The new 2011-2012 symposium arrives at an important time for infectious disease management worldwide.
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