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Oct 03, 2023 344 likes •702 views

What You Need to Know When You What You Need to Know When You Prescribe Fluoroquinolones Fluoroquinolones to to Prescribe Community Patients Community Patients David C. Hooper, M.D. David C. Hooper, M.D. Division of Infectious Diseases

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SLIDE 1

What You Need to Know When You What You Need to Know When You Prescribe Prescribe Fluoroquinolones Fluoroquinolones to to Community Patients Community Patients

David C. Hooper, M.D. David C. Hooper, M.D. Division of Infectious Diseases Division of Infectious Diseases Infection Control Unit Infection Control Unit Massachusetts General Hospital Massachusetts General Hospital Harvard Medical School Harvard Medical School Boston, Massachusetts Boston, Massachusetts

GSK Chair of Infectious Diseases Lesson to Students – Brussels, March 28th, 2007

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SLIDE 2

Sites of Action of Antimicrobial Sites of Action of Antimicrobial Agents in Clinical Use Agents in Clinical Use

Neu HC. Science 1992; 257:1064-73

Topoisomerase IV Linezolid (Oxazolidinone) Daptomycin (Lipopeptide) Telithromycin (Ketolide) Glycylcyclines

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SLIDE 3

Fluoroquinolones Fluoroquinolones Available Available in the United States in the United States

  • Norfloxacin

Norfloxacin ( (Noroxin Noroxin) ) 1986 (PO) 1986 (PO)

  • Ciprofloxacin (

Ciprofloxacin (Cipro Cipro) ) 1987 (PO), 1990 (IV) 1987 (PO), 1990 (IV)

  • Ofloxacin

Ofloxacin ( (Floxin Floxin) ) 1990 (PO), 1992 (IV) 1990 (PO), 1992 (IV)

  • Levofloxacin

Levofloxacin ( (Levaquin Levaquin) ) 1996 (IV & PO) 1996 (IV & PO)

  • Gatifloxacin

Gatifloxacin ( (Tequin Tequin) ) 1999 (IV & PO) 1999 (IV & PO)

  • Moxifloxacin

Moxifloxacin ( (Avelox Avelox) ) 1999 (PO), 2001 (IV) 1999 (PO), 2001 (IV)

  • Gemifloxacin

Gemifloxacin ( (Factive Factive) ) 2003 (PO) 2003 (PO)

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SLIDE 4

Fluoroquinolone Structures

Gemifloxacin

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SLIDE 5

Properties of Newer Quinolones Properties of Newer Quinolones

  • Broad spectrum activity

– Gram-negative bacteria – Improved against Gram-positive bacteria – Improved against Anaerobes

  • Once or twice daily dosing
  • Some with apparent reduced risk of

selection of resistance

  • Broad spectrum activity

– Gram-negative bacteria – Improved against Gram-positive bacteria – Improved against Anaerobes

  • Once or twice daily dosing
  • Some with apparent reduced risk of

selection of resistance

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SLIDE 6

Fluoroquinolones Fluoroquinolones Spectrum of Activity Spectrum of Activity

  • Enterobacteriaceae

Enterobacteriaceae

  • Haemophilus

Haemophilus spp spp. . Neisseria Neisseria spp spp. .

  • Legionella

Legionella, , Mycoplasma Mycoplasma, Chlamydia , Chlamydia [ [Levofloxacin Levofloxacin, , Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin] ]

  • Pseudomonas

Pseudomonas aeruginosa aeruginosa [Ciprofloxacin, [Ciprofloxacin, Levofloxacin Levofloxacin] ]

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SLIDE 7

Fluoroquinolones Fluoroquinolones Spectrum of Activity Spectrum of Activity

  • Staphylococci (MSSA, MSSE) [

Staphylococci (MSSA, MSSE) [Levofloxacin Levofloxacin, , Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin, , Gemifloxacin Gemifloxacin] ]

  • Streptococci (+/

Streptococci (+/-

  • enterococci

enterococci) [ ) [Levofloxacin Levofloxacin, , Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin, , Gemifloxacin Gemifloxacin] ]

  • Anaerobes [

Anaerobes [Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin] ]

  • Mycobacteria

Mycobacteria ( (M. tuberculosis, M.

  • M. tuberculosis, M. kansasii

kansasii, , M.

  • M. fortuitum

fortuitum) [Ciprofloxacin, ) [Ciprofloxacin, Levofloxacin Levofloxacin, , Gatifloxacin Gatifloxacin, , Moxifloxacin Moxifloxacin] ]

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SLIDE 8

General General Clinical Uses of Fluoroquinolones

  • Urinary Tract Infections

Urinary Tract Infections

  • Prostatitis

Prostatitis

  • Sexually Transmitted Diseases

Sexually Transmitted Diseases

  • Gastroenteritis

Gastroenteritis

  • Intraabdominal

Intraabdominal Infections Infections

  • Respiratory Tract Infections

Respiratory Tract Infections

  • Bone & Joint Infections

Bone & Joint Infections

  • Skin & Soft Tissue Infections

Skin & Soft Tissue Infections

  • Other Broad Uses in Hospitalized Patients

Other Broad Uses in Hospitalized Patients

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SLIDE 9

General Clinical Uses of Fluoroquinolones

  • Urinary Tract Infections

Urinary Tract Infections

  • Prostatitis

Prostatitis

  • Sexually Transmitted Diseases

Sexually Transmitted Diseases

  • Gastroenteritis

Gastroenteritis

  • Intraabdominal

Intraabdominal Infections Infections

  • Respiratory Tract Infections

Respiratory Tract Infections

  • Bone & Joint Infections

Bone & Joint Infections

  • Skin & Soft Tissue Infections

Skin & Soft Tissue Infections

  • Other Broad Uses in Hospitalized Patients

Other Broad Uses in Hospitalized Patients

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SLIDE 10

Community Community-

  • Acquired

Acquired Pneumonia Pneumonia

Annually: Annually:

  • 2

2-

  • 3 Million Cases

3 Million Cases

  • ~10 Million Physician Visits

~10 Million Physician Visits

  • 500,000 Hospitalizations

500,000 Hospitalizations

– – 258 per 100,000 population 258 per 100,000 population – – 962 per 100,000 persons 962 per 100,000 persons ≥ ≥ 65 65 yo yo

  • 45,000 Deaths

45,000 Deaths

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SLIDE 11

Microbial Causes of Community Microbial Causes of Community-

  • Acquired Pneumonia

Acquired Pneumonia

  • Streptococcus

Streptococcus pneumoniae pneumoniae

  • Haemophilus

Haemophilus influenzae influenzae

  • Moraxella

Moraxella catarrhalis catarrhalis

  • Staphylococcus

Staphylococcus aureus aureus

  • Klebsiella

Klebsiella pneumoniae pneumoniae

  • Other Gram

Other Gram-

  • negative bacilli

negative bacilli

  • Anaerobic bacteria

Anaerobic bacteria (aspiration) (aspiration)

  • Mycoplasma

Mycoplasma pneumoniae pneumoniae

  • Chlamydia

Chlamydia pneumoniae pneumoniae

  • Legionella

Legionella spp spp. .

  • Influenza virus

Influenza virus

  • Others:

Others: mycobacteria mycobacteria, fungi, , fungi, Nocardia Nocardia spp spp., ., Pneumocystis Pneumocystis carinii carinii, other , other viruses viruses

  • None found ~ 50%

None found ~ 50%

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SLIDE 12

Streptococcus Streptococcus pneumoniae pneumoniae

Otitis Otitis media media 7,000,000 cases 7,000,000 cases Pneumonia Pneumonia 500,000 cases 500,000 cases Bacteremia Bacteremia 50,000 cases 50,000 cases Meningitis Meningitis 3,000 cases 3,000 cases Deaths Deaths 40,000 40,000 Mortality rate Mortality rate for for bacteremia bacteremia 30 30 -

  • 40%

40%

United States data from CDC United States data from CDC

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SLIDE 13

5 10 15 20 25 30

1979- 1987 1991- 92 1996 1998 Year

* *MIC 0.1

MIC 0.1 -

  • 1.0

1.0 µ µg/ml g/ml (intermediate) + (intermediate) + ≥ ≥ 2.0 2.0 µ µg/ml (high g/ml (high-

  • level) resistance

level) resistance Applebaum PC et al. Clin Infect Dis. 1992;15:77 Breiman RF et al. JAMA. 1994;271:1831 Doem GV et al. Antimicrob Ag Chemother. 1996;40:1208 Whitney CG et al. N. Engl. J. Med. 2000;343:1917 Isolates Resistant to Isolates Resistant to Penicillin* (%) Penicillin* (%)

Penicillin Penicillin-

  • Non

Non-

  • Susceptible

Susceptible Streptococcus Streptococcus pneumoniae pneumoniae in the in the United States United States

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SLIDE 14

Cross Resistance Among Penicillin Cross Resistance Among Penicillin-

  • Resistant

Resistant Strains of Strains of Streptococcus Streptococcus pneumoniae pneumoniae

Antimicrobial % Resistant to Other Antimicrobial Antimicrobial % Resistant to Other Antimicrobial Penicillin Penicillin Penicillin Penicillin Penicillin Penicillin Susceptible Intermediate Resistant Susceptible Intermediate Resistant

(n=2636) (n=356, (n=2636) (n=356, 10% 10%) (n=483, ) (n=483, 14% 14%) ) Amoxicillin Amoxicillin 0.0 0.0 1.8 1.8 82.2 82.2 Cefuroxime Cefuroxime 0.1 0.1 34.8 34.8 100 100 Cefotaxime Cefotaxime 0.0 0.0 2.8 2.8 42.4 42.4 Meropenem Meropenem 0.0 0.8 0.0 0.8 52.0 52.0 Erythromycin 3.2 Erythromycin 3.2 35.1 35.1 61.3 61.3 TMP TMP-

  • SMX

SMX 6.6 6.6 49.4 49.4 92.3 92.3 Tetracycline 1.3 Tetracycline 1.3 19.1 25.5 19.1 25.5 Whitney CG et al. N. Engl. J. Med. 2000;343:1917-24

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SLIDE 15

Cross Resistance Among Penicillin Cross Resistance Among Penicillin-

  • Resistant

Resistant Strains of Strains of Streptococcus Streptococcus pneumoniae pneumoniae

Antimicrobial % Resistant to Other Antimicrobial Antimicrobial % Resistant to Other Antimicrobial Penicillin Penicillin Penicillin Penicillin Penicillin Penicillin Susceptible Intermediate Resistant Susceptible Intermediate Resistant

(n=2636) (n=356) (n=483) (n=2636) (n=356) (n=483)

Chloramphenicol Chloramphenicol 0.4 0.4 6.7 6.7 14.7 14.7 Clindamycin Clindamycin 0.5 0.5 10.7 10.7 12.2 12.2 Rifampin Rifampin 0.2 0.2 0.0 0.0 0.2 0.2 Levofloxacin Levofloxacin 0.1 0.3 0.1 0.3 0.7 0.7 Quinupristin Quinupristin-

  • dalfopristin

dalfopristin 0.0 0.6 0.0 0.6 0.2 0.2

Whitney CG et al. N. Engl. J. Med. 2000;343:1917-24

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SLIDE 16

Pharmacokinetic Properties of Pharmacokinetic Properties of Oral Oral Fluoroquinolones Fluoroquinolones

Drug Dose Drug Dose C Cmax

max

t t½

½

Renal Renal

(mg (mg -

  • (

(μ μg/ml) (h) g/ml) (h) Clearance

Clearance

frequency) frequency) (% of total) (% of total) Ciprofloxacin 500 BID 2.2 3.3 50 Ciprofloxacin 500 BID 2.2 3.3 50 Levofloxacin Levofloxacin 500 QD 5.7 6 500 QD 5.7 6-

  • 8 65

8 65 750 QD 750 QD 8.6 8.6 Gatifloxacin Gatifloxacin 400 QD 4.1 7 400 QD 4.1 7-

  • 8 80

8 80 Moxifloxacin Moxifloxacin 400 QD 4.5 13 22 400 QD 4.5 13 22 Gemifloxacin Gemifloxacin 320 QD 320 QD 1.8 1.8 7 30

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SLIDE 17

Activity of Quinolones Against 75 Ciprofloxacin-Resistant Isolates of Streptococcus pneumoniae

Quinolone Quinolone Cumulative % Isolates at MIC ( Cumulative % Isolates at MIC (μ μg/ml) g/ml) ≤ ≤0.06 0.12 0.06 0.12-

  • 0.25 0.5

0.25 0.5-

  • 1 2

1 2-

  • 4 8

4 8-

  • 16 32

16 32-

  • 64

64 Levofloxacin Levofloxacin 16 67 95 100 16 67 95 100 Gatifloxacin Gatifloxacin 4 64 93 100 4 64 93 100 Moxifloxacin Moxifloxacin 56 71 97 100 56 71 97 100 Gemifloxacin Gemifloxacin 61 92 100 61 92 100

Chen DK et al. 1999. N Engl J Med. 341:233-9

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SLIDE 18

Pharmacodynamic Parameters

Αmsden GW et al. In: Mandell, Bennett, Dolin. Principles and Practice of Infectious Diseases, 5th edition, p. 253, 1999.

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SLIDE 19

Pharmacodynamics of Ciprofloxacin in Patients with Pneumonia

Forrest A et al. Antimicrob Agents Chemother. 37:1073 (1993)

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SLIDE 20

Randomized Comparison of Randomized Comparison of Levofloxacin Levofloxacin with with Ceftriaxone/Cefuroxime Ceftriaxone/Cefuroxime for Treatment for Treatment

  • f Community
  • f Community-
  • Acquired Pneumonia

Acquired Pneumonia

Pathogen No. (%) of Patients Responding to: Pathogen No. (%) of Patients Responding to: Levofloxacin Levofloxacin Ceftriaxone/Cefuroxime Ceftriaxone/Cefuroxime

Cured Improved Failed Cured Improved Failed Cured Improved Failed Cured Improved Failed S.

  • S. pneumoniae

pneumoniae 23(77) 7(23) 0 24(73) 7(21) 2(6) 23(77) 7(23) 0 24(73) 7(21) 2(6) [ [bacteremic bacteremic] 7(78) 2(22) 0 4(50) 4(50) ] 7(78) 2(22) 0 4(50) 4(50) 0 H.

  • H. influenzae

influenzae 24(80) 6(20) 0 17(71) 2(8) 5 24(80) 6(20) 0 17(71) 2(8) 5(21) (21) C.

  • C. pneumoniae

pneumoniae 34(72) 12(26) 1(2) 34(63) 16(30) 4(7) 34(72) 12(26) 1(2) 34(63) 16(30) 4(7) M.

  • M. pneumoniae

pneumoniae 15(79) 4(21) 0 17(77) 5(22) 0 15(79) 4(21) 0 17(77) 5(22) 0 L.

  • L. pneumophila

pneumophila 4(80) 1(20) 0 2(66) 0 1 4(80) 1(20) 0 2(66) 0 1(33) (33)

File TM et al. Antimicrob Agents Chemother. 41:1965 (1997)

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SLIDE 21

Comparison of High Comparison of High-

  • Dose Short

Dose Short-

  • Course with

Course with Conventional Conventional-

  • Course

Course Levofloxacin Levofloxacin for for Community Community-

  • Acquired Pneumonia

Acquired Pneumonia

Dunbar LM et al. Clin Infect Dis 2003; 37: 752 Clinical Responses by Severity Clinical Responses by Severity

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SLIDE 22

Dunbar LM et al. Clin Infect Dis 2003; 37: 752

Comparison of High Comparison of High-

  • Dose Short

Dose Short-

  • Course with

Course with Conventional Conventional-

  • Course

Course Levofloxacin Levofloxacin for for Community Community-

  • Acquired Pneumonia

Acquired Pneumonia

Clinical Responses by Pathogen Clinical Responses by Pathogen

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SLIDE 23

Moxifloxacin Moxifloxacin vs vs Amoxicillin Amoxicillin-

  • Clavulanate

Clavulanate in Community in Community-

  • Acquired Pneumonia

Acquired Pneumonia

Moxifloxacin 400 mg QD IV → PO Amox-clav 1.2g TID IV → 625 mg TID-QID PO (± clarithromycin) Finch R et al. Antimicrob Agents Chemother. 2002; 46:1746-54

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SLIDE 24

Moxifloxacin Moxifloxacin vs vs Amoxicillin Amoxicillin-

  • Clavulanate

Clavulanate in Community in Community-

  • Acquired Pneumonia

Acquired Pneumonia

Eradication Eradication Moxifloxacin Moxifloxacin Amox Amox-

  • Clav

Clav

% (n/N) % (n/N) % (n/N) % (n/N) Total Total 94 (60/64) 94 (60/64) 82 (58/71) 82 (58/71) S.

  • S. pneumoniae

pneumoniae Sputum Sputum 100 (18/18) 100 (18/18) 77 (17/22) 77 (17/22) Blood Blood 100 (11/11) 100 (11/11) 90 (9/10) 90 (9/10) H.

  • H. influenzae

influenzae 100 (12/12) 100 (12/12) 90 (9/10) 90 (9/10) M.

  • M. pneumoniae

pneumoniae 100 (13/13) 100 (13/13) 95 (16/17) 95 (16/17)

Finch R et al. Antimicrob Agents Chemother. 2002; 46:1746-54

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SLIDE 25

Cox Model for Mortality Based Cox Model for Mortality Based

  • n Initial Therapy of Pneumonia
  • n Initial Therapy of Pneumonia

Fluoroquinolone 3rd-Gen Ceph 2nd- or 3rd-Gen Ceph + Macrolide

Gleason PP et al. Arch Intern Med. 1999; 159:2562-72.

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SLIDE 26

IDSA Guidelines for Initial Empiric IDSA Guidelines for Initial Empiric Treatment of Patients with Treatment of Patients with Community Community-

  • Acquired Pneumonia

Acquired Pneumonia

Outpatients Outpatients

  • Previously healthy without use of antimicrobials

Previously healthy without use of antimicrobials within 3 months within 3 months (except in areas with >25%

(except in areas with >25% macrolide macrolide resistance) resistance) – – a a macrolide macrolide or

  • r doxycycline

doxycycline

  • Patients with co

Patients with co-

  • morbid illness or prior antimicrobials

morbid illness or prior antimicrobials (c (chronic heart, lung, or liver disease, diabetes, malignancy,

hronic heart, lung, or liver disease, diabetes, malignancy, immunosuppression immunosuppression or antimicrobials within last 3 mo)

  • r antimicrobials within last 3 mo)

– – Respiratory Respiratory fluoroquinolone fluoroquinoloneA

A OR

OR – – β β-

  • Lactam

Lactam plus a plus a macrolide macrolide

Mandell LA et al. Clin Infect Dis 2007; 44:S27

A A[levofloxacin

[levofloxacin (750 mg), (750 mg), moxifloxacin moxifloxacin (400 mg), or (400 mg), or gemifloxacin gemifloxacin (320mg)] (320mg)]

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SLIDE 27

IDSA Guidelines for Initial Empiric IDSA Guidelines for Initial Empiric Treatment of Patients with Treatment of Patients with Community Community-

  • Acquired Pneumonia

Acquired Pneumonia

Hospitalized patients Hospitalized patients (non (non-

  • ICU)

ICU)

  • Respiratory

Respiratory fluoroquinolone fluoroquinoloneA

A OR

OR

  • β

β-

  • Lactam

Lactam plus a plus a macrolide macrolide Hospitalized patients Hospitalized patients (ICU) (ICU)

  • (

(Cefotaxime Cefotaxime, , ceftriaxone ceftriaxone, or , or ampicillin ampicillin-

  • sulbactam

sulbactam) plus ( ) plus (azithromycin azithromycin or respiratory

  • r respiratory

fluoroquinolone fluoroquinolone) )

Mandell LA et al. Clin Infect Dis 2007; 44:S27

A A[levofloxacin

[levofloxacin (750 mg), (750 mg), moxifloxacin moxifloxacin (400 mg), or (400 mg), or gemifloxacin gemifloxacin (320mg)] (320mg)]

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SLIDE 28

IDSA Guidelines for Initial Empiric IDSA Guidelines for Initial Empiric Treatment of Patients with Treatment of Patients with Community Community-

  • Acquired Pneumonia

Acquired Pneumonia

Special considerations Special considerations

  • If

If Pseudomonas Pseudomonas aeruginosa aeruginosa

– – ( (Piperacillin Piperacillin-

  • tazobactam

tazobactam, , cefepime cefepime, , imipenem imipenem, or , or meropenem meropenem) ) plus (ciprofloxacin or plus (ciprofloxacin or levofloxacin levofloxacin (750 mg) OR (750 mg) OR – – ( (Piperacillin Piperacillin-

  • tazobactam

tazobactam, , cefepime cefepime, , imipenem imipenem, or , or meropenem meropenem) ) plus plus aminoglycoside aminoglycoside plus ( plus (azithromycin azithromycin or respiratory

  • r respiratory

fluoroquinolone fluoroquinoloneA

A)

)

  • If community

If community-

  • acquired MRSA

acquired MRSA

– – Add Add vancomycin vancomycin or

  • r linezolid

linezolid

A A[levofloxacin

[levofloxacin (750 mg), (750 mg), moxifloxacin moxifloxacin (400 mg), or (400 mg), or gemifloxacin gemifloxacin (320mg)] (320mg)]

Mandell LA et al. Clin Infect Dis 2007; 44:S27

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SLIDE 29

Fluoroquinolones Fluoroquinolones Adverse Effects Adverse Effects

  • Nausea, vomiting, diarrhea, taste perversion

Nausea, vomiting, diarrhea, taste perversion

  • Insomnia, HA, dizziness (

Insomnia, HA, dizziness (trovafloxacin trovafloxacin), ), psychiatric, seizures [inhibit GABA binding to psychiatric, seizures [inhibit GABA binding to receptors] receptors]

  • Rash, interstitial nephritis, photosensitivity

Rash, interstitial nephritis, photosensitivity ( (lomefloxacin lomefloxacin, , sparfloxacin sparfloxacin) )

  • Hepatotoxicity

Hepatotoxicity ( (trovafloxacin trovafloxacin) )

  • Dysglycemia

Dysglycemia ( (gatifloxacin gatifloxacin) )

  • QT prolongation (

QT prolongation (sparfloxacin sparfloxacin > > moxifloxacin moxifloxacin) )

  • Cartilage erosions in juvenile animals

Cartilage erosions in juvenile animals

  • Tendinitis

Tendinitis

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SLIDE 30

Temporal Trends in Temporal Trends in Quinolone Quinolone Resistance in Resistance in S.

  • S. pneumoniae

pneumoniae

Chen DK et al. 1999. N Engl J Med. 341:233-9

1997 1998

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SLIDE 31

Development of Bacterial Resistance Development of Bacterial Resistance to to Fluoroquinolones Fluoroquinolones

Staphylococci (MRSA, MRSE) Staphylococci (MRSA, MRSE) Pseudomonas Pseudomonas aeruginosa aeruginosa 60 60-

  • 95%

95% 5 5-

  • 30%

30% Campylobacter Campylobacter jejuni jejuni 3 3-

  • 50%

50% Escherichia coli Escherichia coli 8 8-

  • 26%

26% Neisseria Neisseria gonorrheae gonorrheae 6 6-

  • 70%

70% Streptococcus Streptococcus pneumoniae pneumoniae 1 1-

  • 14%

14%

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SLIDE 32

Mechanisms of Resistance Mechanisms of Resistance to to Fluoroquinolones Fluoroquinolones

  • Chromosomal mutations

Chromosomal mutations

– – Alterations in DNA Alterations in DNA gyrase gyrase and/or and/or topoisomerase topoisomerase IV IV – – Active drug efflux (MDR pumps) +/ Active drug efflux (MDR pumps) +/-

  • reduced

reduced porin porin diffusion diffusion channels channels

  • Plasmid

Plasmid-

  • mediated resistance (many enteric bacteria)

mediated resistance (many enteric bacteria)

– – QnrA QnrA, B, S , B, S – – protection of protection of gyrase gyrase and and topoisomerase topoisomerase IV IV – – Aac(6 Aac(6’ ’) )-

  • Ib

Ib-

  • cr

cr – – acetylation acetylation of ciprofloxacin and

  • f ciprofloxacin and norfloxacin

norfloxacin by a variant by a variant aminoglycoside aminoglycoside acetyltransferase acetyltransferase (also causes (also causes resistance to resistance to tobramycin tobramycin, , amikacin amikacin, and , and kanamycin kanamycin) ) – Usually on plasmids with multiple resistance determinants

slide-33
SLIDE 33

Pharmacodynamics Pharmacodynamics of

  • f Quinolone

Quinolone-

  • Resistant Mutant Selection

Resistant Mutant Selection

Drlica K and Zhao X. Clin Infect Dis. 2007; 44:681

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SLIDE 34

Pharmacodynamic Pharmacodynamic Factors Factors Affecting Risk of Selection of Affecting Risk of Selection of Quinolone Quinolone Resistance Resistance

  • Selecting Drug Concentration

Selecting Drug Concentration in Vitro in Vitro

  • C

Cmax

max/MIC

/MIC -

  • Animal Models

Animal Models

  • AUC/MIC

AUC/MIC -

  • Human Use

Human Use

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SLIDE 35

Limiting Bacterial Resistance Limiting Bacterial Resistance to to Fluoroquinolones Fluoroquinolones

  • Monitor Resistance

Monitor Resistance

  • Good Infection Control to Limit Spread

Good Infection Control to Limit Spread

  • Focused and Balanced Use to Limit

Focused and Balanced Use to Limit Selective Pressures Selective Pressures

  • Adequate Dosing to Limit Mutant

Adequate Dosing to Limit Mutant Selection Selection