Table 1.  In Vitro Activity Profiles of the Fluoroquinolones (μg/mL)

                                         Ciprofloxacin                Levofloxacin                 Gatifloxacin                     Moxifloxacin                 Gemifloxacin

Organism

MIC50

MIC90

MIC50

MIC90

MIC50

MIC90

MIC50

MIC90

MIC50

MIC90

Gram-Negatives

 

 

 

 

 

 

 

 

 

 

Acinetobacter baumannii

0.5-32

>16

0.25-4

8-16

0.12-4

8-16

0.12-8

16-32

0.12-8

16 - >16

Enterobacter cloacae

0.008-0.03

0.016-1

0.03 - 0.06

0.03-1

0.03-0.06

0.03-1

0.06

0.125-0.25

0.016-0.03

0.03-0.5

Escherichia coli

0.008- 0.03

0.03-1

0.015- 0.03

0.06-0.5

0.016-0.3

0.03-0.5

0.03-0.06

0.06-1

0.008- 0.016

0.03-0.5

Haemophilus influenzae

0.008-0.015

0.015-0.03

0.015

0.015-0.06

0.008-0.015

0.015-0.03

0.015-0.03

0.06-0.03

0.002-0.004

0.008-0.03

Klebsiella pneumoniae

0.016- 0.06

0.06-2

≤0.03-0.06

0.25-2

0.03-0.06

0.06-1

0.06- 0.25

0.125-1

0.03-0.06

0.125-1

Moraxella catarrhalis

0.03-0.06

0.03-0.06

0.03-0.06

0.06

0.03

0.03-0.06

0.03-0.12

0.06-0.12

0.008-0.015

0.008-0.03

Morganella morganii

0.008-0.016

0.015-2

0.031

0.125- 0.25

0.25

0.25

0.12-0.25

0.25-0.5

0.06

0.125-4

Neisseria gonorrhoeae

0.004-0.5

0.004-0.5

0.008-0.5

0.12-0.5

0.12

0.25

0.008-0.25

0.015-0.5

0.004-0.12

0.06-0.5

Neisseria meningitidis

≤0.002-0.008

0.004-0.008

0.008

0.008

0.004-0.008

0.008

0.008

0.008-0.015

0.004-0.008

0.008

Proteus mirabilis

0.03-0.06

0.03- 2

0.03-0.5

0.12-2

0.12-0.25

2-4

0.25-1

0.25-8

0.12-0.25

0.25-8

Pseudomonas aeruginosa

≤0.25-1

4 - >16

1-4

>4 - 16

1-4

>4

2-16

8

0.5-4

>4 - >16

Serratia

marcescens

0.06-0.25

0.5-4

0.125

0.25-2

0.25

2

0.25

4

0.125-0.25

1-2

Salmonella spp.

0.016-0.12

0.03-

0.25

0.03-0.06

0.25 - 0.5

0.03- 0.06

0.06-0.25

0.12

1

0.016-0.03

0.016- 0.12

Stenotrophomonas maltophilia

2-4

8-16

0.5-1

4-8

0.5-1

4-8

0.5-1

2-4

0.5-2

4-8

Gram-Positives

 

 

 

 

 

 

 

 

 

 

Staphylococcus aureus

0.5-1

0.5 - >4

0.125-0.25

0.25 - >4

0.06-0.12

0.12 - >4

0.06

0.06-2

NA

0.06-8

MS S. aureus

0.25-1

0.5-4

0.12-0.25

0.25-2

0.06-0.12

0.125-0.5

0.03-0.12

0.06-0.25

0.015-0.06

0.03-0.12

MR S. aureus

1 - >16

16 - >128

0.25-32

8 - >128

0.125-8

4 - >128

0.06 - 2

2-128

0.03-4

2 - >128

Streptococcus pneumoniae

1-2

2-16

0.5-1

1-2

0.25-0.5

0.5

0.03-0.25

0.12-0.25

0.015-0.03

0.03-0.06

Penicillin susceptible

1-2

2-4

0.5-1

1-2

0.25

0.5

0.125-0.25

0.25

0.015-0.03

0.03-0.06

Penicillin intermediate

1-2

2-4

0.5-1

1-2

0.25

0.5

0.125-0.25

0.12-0.25

0.015-0.03

0.03-0.06

Penicillin

resistant

1-2

2-4

0.5-1

1-2

0.25-0.5

0.25-0.5

0.125-0.25

0.12-0.25

0.015-0.03

0.03-0.06

Viridans Streptococcus

1-2

4

1

1-2

0.25-0.5

0.5-1

0.25

0.25-0.5

0.03-0.06

0.06-0.25

S. agalactiae

0.25-1

1-2

0.5

0.5-1

0.25-0.5

0.25-0.5

0.125 0.25

0.25

0.03-0.06

0.03-0.25

S. pyogenes

0.25-1

1

0.25-0.5

0.5-1

0.12-0.25

0.25-0.5

0.06-0.25

0.25-0.5

0.016-0.06

0.03-0.25

Enterococcus faecalis

0.5-2

1 - >16

1

8 - >16

0.5-1

1-16

0.12-0.5

0.25 - 4

0.06-0.25

2 - 4

Enterococcus faecium

2 - >16

4 - >128

8->16

8->16

2 - 16

16

2 - 32

2 - >32

4 - >16

4 - >16

Anaerobes

 

 

 

 

 

 

 

 

 

 

Bacteroides fragilis

4

32

1-2

4-16

0.25-1

1-4

0.125-1

1-4

0.5 - 1

2 - 16

Clostridium difficile

8-16

16-64

4

4 - >16

1

2

1

2

1-2

2 - >16

Fusobacterium spp.

1- 4

2-16

1

1-8

0.25-1

0.25-8

0.25-0.5

2-4

≤0.25 - 4

0.5-8

Peptostreptococcus spp.

1

2

0.5-4

4

0.5

1

0.06-0.5

0.12-1

0.03-0.12

0.06-2

Porphyromonas spp.

0.5

2

0.25

1

0.125

0.25

0.03-0.25

0.03-0.25

0.06

0.125

Prevotella spp.

1-4

2-64

0.5-1

1-8

0.25-0.5

0.5-4

0.125-0.5

0.25-2

1-4

2-16

Miscellaneous

 

 

 

 

 

 

 

 

 

 

Mycobacterium tuberculosis

0.125-2

0.125-4

0.125-0.5

0.125-1

0.03-0.12

0.03-0.25

0.25-0.6

0.125-1

4

8

Mycoplasma pneumoniae

1

1-2

0.25-0.5

0.5-1

0.06

0.12

0.06

0.06-0.12

NA

0.25

Chlamydia pneumoniae

0.5

2

0.25-0.5

0.5-1

0.06-0.25

0.125-0.25

0.06-1

0.5-1

0.25

0.25

Legionella pneumophila

0.016-0.03

0.016-0.06

0.008-0.016

0.008-0.016

0.008-0.016

0.016-0.03

0.008-0.016

0.008-0.03

0.008-0.03

0.016-0.03

NA: not available

Complied from references (8, 11, 24, 25, 31, 36, 41, 54-57, 65, 72, 75, 81, 82, 85, 96-99, 101, 105, 107, 109-113, 119, 123, 128, 132-134, 142, 165, 173, 190, 215, 216, 218, 219, 222, 224, 225, 232, 237, 249, 255, 271, 272, 281, 285)

 

Table 2.  Pharmacokinetic Parameters of the Fluoroquinolones

 

Parameter

Norfloxacin

Ciprofloxacin

Oflox/Levofloxacin

Gatifloxacin

Trovafloxacin

Moxifloxacin

Gemifloxacin

Dose (mg)

400

750

400/500

400

300

400

320

Peak (mg/mL)

1.5

3.5

4.0/6.0

3.4

4.0

4.5

1.6

Peak / 100 mg dose

0.38

0.46

1.0/1.2

0.85

1.32

1.12

0.5

Protein bound (%)

15

25

25

18

70

50

60

Vdss (L/kg)

1.7

3.2

1.45

1.7

1.1

2.7

4.18

t (h)

(CrCl 100 mL/min)

3.3

4.0

6.0

8.4

10.0

12.7

6.1

t (h)

(CrCl 10 mL/min)

8.0

10.0

30.0

>40

12

14.5

NA

AUC (mg∙h/mL)

13.6

29

38/58

32

41.4

48.0

9.1

AUC / 100 mg dose

1.7

1.9

11.7

8

13.8

12

2.8

Clrenal (mL/min)

234

250

190

NA

10

43

134

% Nonrenal

60

40

5

10

90

80

64

% Renal

40

60

95

90

10

20

22

Bioavailability (%)

40

70

99

96

88

86

71

 

Compiled from references: (10, 32, 45, 74, 100, 114, 144, 146, 150, 180, 181, 186, 189, 220, 221, 242, 248, 253, 259, 269, 279, 287)

 

 

Table 3.  Tissue Penetration of the Fluoroquinolones

Site

Dose

Route

Frequency

Time to Ctissue

Conc. Tissue

Time to Cplasma

Conc. Plasma

Reference

Ciprofloxacin

 

 

 

 

 

 

 

 

Bile

500 mg

po

bid x 6

25-26 h

4.5 mg/L

4h

2.5

(64)

Blister, suction

500 mg

 

1 x

 

84.70%

 

2.26

(145)

Lung, parenchyma

200 mg

iv

1 x

 

3.4 mcg/g

 

0.6

(44)

Lung, pleura

200 mg

iv

1 x

 

1.7 mcg/g

 

0.6

(44)

Muscle, heart valve

750 mg

po

q 12h x 4

1-3 h

8.3/3.1 mcg/g

 

11.59/3.95

(170)

Muscle, myocardium

400 mg

iv

1 x

1 h

31.6/25 mcg/g

 

6.19/1.73

(170)

Prostate, TURP

200 mg

po

tid x 9

5.5 h

1.32/0.64

5.5 h

0.65/0.31

(177)

Levofloxacin

 

 

 

 

 

 

 

 

Bile

100 mg

po

1 x

2-6 h

0.49/5.63

2-6 h

0.55/1.63

(257)

Norfloxacin

 

 

 

 

 

 

 

 

Prostate, TURP

200 mg

po

tid x 5

 

4.42/1.94

(2.45/7.76) intraoperative

 

2.89/2.34

(0.87/8.33) intraoperative

(283)

Ofloxacin

 

 

 

 

 

 

 

 

Bone

300 mg

po

1 x

1 h

1.58/0.06 mcg/g

1 h

2.61/0/17

(194)

Lung, parenchyma

600 mg

po

1 x

2 h

17.7/9.2 mcg/g

2 h

8.7/4.2

(275)

Muscle, myocardium

400 mg

iv

1 x

1 h

8.89/2.16

 

15.9/2.5

(170)

Prostate, TURP

200 mg

po

tid x 5

 

5.51/1.79

(3.62-7.19) intraoperative

 

5.36/1.28

(3.12-8.24)

30 min preop

(283)

Moxifloxacin

 

 

 

 

 

 

 

 

Alveolar macrophages

400 mg

po

1 x

2.2 h

56.7

2.2 h

3.2

(247)

Bronchial mucosa

400 mg

po

1 x

2.2 h

1.29

2.2 h

3.2

(247)

Epithelial lining fluid

400 mg

po

1 x

2.2 h

20.7

2.2 h

3.2

(247)

Maxillary sinus mucosa

400 mg

po

qd x 5d

3 h

7.48

3 h

3.58

(87)

Blister

400 mg

iv

1 x

5.6 h

1.7

1 h

3.7

(178)

Skeletal muscle

400 mg

iv

1 x

1.8 h

1.2

1 h

3.7

(178)

Subcutaneous adipose

400 mg

iv

1 x

2 h

1.0

1 h

3.7

(178)

Gemifloxacin

 

 

 

 

 

 

 

 

Alveolar macrophages

320 mg

po

1 x

 

107

 

1.4

(203)

Bronchial mucosa

320 mg

po

1 x

 

9.52

 

1.4

(203)

Epithelial lining fluid

320 mg

po

1 x

 

2.69

 

1.4

(203)

Blister

320 mg

po

1 x

3.4 h

0.74

1.2 h

2.3

(86)

Abbreviations:  bid = twice daily; iv = intravenously; po = orally; qd = once daily; tid = three times daily

 

 

Table 4.  Clinical Indications for the Fluoroquinolones and Dosage Regimens

Indication

Agent

Regimen

Respiratory Infections

 

 

Acute community-acquired pneumonia

Moxifloxacin

400 mg q24h iv/po  x 7-14 days

 

Gemifloxacin

320 mg q24h po x 7 days

 

Gatifloxacin

400 mg q24h iv/po x 7-14 days

 

Ofloxacin

400 mg q12h iv/po x 10 days

 

Levofloxacin

500 mg q24 iv/po x 7-14 days

750 mg q24 iv/po  x 5 days

Lower Respiratory Tract Infections

Ciprofloxacin

500-750 mg q12h po / 400 mg q8-12h iv x 7-14 days

Acute Maxillary Sinusitis

Moxifloxacin

400 mg q24 iv/po  x 5 days

 

Ciprofloxacin

500 mg po q12h po / 400 mg q12h iv x 10 days

 

Levofloxacin

500 mg q12h iv/po x 10-14 days

 

Gatifloxacin

400 mg q24h iv/po x 10 days

Acute bacterial exacerbations of chronic bronchitis

Moxifloxacin

400 mg q24h iv/po x 5 days

 

Gemifloxacin

320 mg q24h po x 5 days

 

Levofloxacin

500 mg q24h iv/po x 7 days

 

Ofloxacin

400 mg q12h iv/po x 10 days

 

Gatifloxacin

400 mg q24h iv/po x 5 days

Nosocomial pneumonia

Ciprofloxacin +/- another agent

400 mg q8 iv x 10-14 days

 

Levofloxacin +/- another agent

750 mg q24h iv/po x 7-14 days

Urinary Tract Infections (UTI)

 

 

Acute Uncomplicated UTIs

Ciprofloxacin

250 mg q12h po x 3 days

 

Levofloxacin

250 mg q24h iv/po x 3 days

 

Gatifloxacin

400 mg iv/po single dose or 200 mg q24h iv/po x 3 days

 

Norfloxacin

400 mg q12h po x 3-10 days

 

Ofloxacin

200 mg q12h iv/po x 3-7 days

Complicated UTI and pyelonephritis

Levofloxacin

250 mg q24h iv/po x 10 days

 

Gatifloxacin

400 mg q24h iv/po x 7-10 days

 

Ciprofloxacin

500 mg q 12h po / 400 mg q12h iv x 7-14 days

 

Ofloxacin

200 mg q12h iv/po x 10 days

 

Norfloxacin

400 mg q12h po x 10-21 days

Prostatitis

Levofloxacin

500 mg q24h iv/po x 28 days

 

Ciprofloxacin

500 mg q12 h po / 400 mg q12h iv x 28 days

 

Norfloxacin

400 mg q12h po x 28 days

 

Ofloxacin

300 mg q12h iv/po x 6 weeks

Venereal Diseases

 

 

Uncomplicated gonococcal infections

Ciprofloxacin

500 mg po single dose

(Avoid in Asia/Pacific, Hawaii and California)

Ofloxacin

400 mg iv/po single dose

 

Levofloxacin

250 mg iv/po single dose

 

Gatifloxacin

400 mg iv/po single dose

 

Norfloxacin

400 mg po single dose

Urethritis due to C. trachomatis

Ofloxacin

300 mg q12h iv/po x 7 days

 

Levofloxacin

500 mg q24h x 7 days

Acute PID

Ofloxacin (+ metronidazole)

400 mg q12h iv/po x 10-14 days

 

Levofloxacin (+ metronidazole)

500 mg q24h iv/po x 10-14 days

Chancroid

Ciprofloxacin

500 mg q12h po x 3 days

Epididymitis due to enteric gram-negative organisms

Ofloxacin

300 mg q12h iv/po x 10 days

 

Levofloxacin

500 mg q24h iv/po x 10 days

Skin and Bone

 

 

Uncomplicated skin and skin structure infection

Moxifloxacin

400 mg q24h x 7 days

 

Ciprofloxacin

500-750 mg q12h po x 7-14 days

400 mg q8-12h iv

 

Levofloxacin

500 mg q24h iv/po x 7-10 days

 

Ofloxacin

400 mg q12h iv/po x 10 days

 

Gatifloxacin

400 mg q24h iv/po x 7-10 days

Complicated skin and skin structure infection

Levofloxacin

750 mg q24h iv/po x 7-14 days

Bone and Joint infection

Ciprofloxacin

500-750 mg q12h po x 4-6 weeks

400 mg q 8-12h iv

Abdominal infections

 

 

Intra-abdominal infection

Ciprofloxacin (+ metronidazole)

500 mg q12h po x 7-14 days

400 mg q12h iv

Infectious diarrhea

Ciprofloxacin

500 mg q12h x 3-5 days (current recommendations)

500 mg q12h po x 5-7 days (labeled)

 

Ofloxacin

300 mg q 12h x 3-5 days

 

Norfloxacin

400 mg q12h x 3-5 days

Typhoid Fever

Ciprofloxacin

500 mg q12h po x 10 days

Inhalational anthrax (post-exposure)

Ciprofloxacin

500 mg q 12h po x 60 days

 

Empiric therapy in febrile neutropenia

Ciprofloxacin (+ piperacillin)

400 mg q8h iv

 

 

 

Compiled from references (60, 201-206)

 

 

Table 5.  Side Effect and Drug Interaction Profile of the Fluoroquinolones

Parameter

Norfloxacin

Ciprofloxacin

Oflox/Levofloxacin

Gatifloxacin

Trovafloxacin

Moxifloxacin

Gemifloxacin

GI Upset

+2

+2

+1

+3

+2

+3

+2

Photosensitivity

0

0

+1

+0

0

0

0

CNS Effects

+1

+1

+2

+2

+3

+1

+1

QTc prolongation

+1

+1

+1

+1

+1

+1

+1

Theophylline interaction

+1

+1

+1

0

0

0

0

Cation interaction

+4

+4

+2

+3

+1

+3

+4

Warfarin interaction

+2

+1

0

0

0

0

0

For interactions: 0, none; +1, 1-20% change; +2, 20-40% change; +3, 40-60% change; +4, > 60% change.  For GI upset,QTc prolongation, photosensitivity, and CNS effects: 0, none; +1, 1-3%; +2, 3-5%; +3, 5-10%; +4, > 10%.

Adapted from references:(21, 46, 185, 195, 201-207)

 

 

Table 6.  Dosing During Continuous Renal Replacement Therapy  (Ciprofloxacin)

 

CVVH (Continuous venovenous hemofiltration): 200mg IV q12h

CVVHD (Continuous venovenous hemodialysis): 200-40mg IVq12h

CVVHDF (Continuous venovenous hemodiafiltration) 200-400mg g IV q12h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD

or CVVHDF which combine dialysis with fluid removal.

 

 

Table 7:  Dosing during Continuous Renal Replacement Therapy(Moxifloxacin)

 

CVVH (Continuous venovenous hemofiltration): 400mg q12h

CVVHD (Continuous venovenous hemodialysis): 400mg IV q12h

CVVHDF (Continuous venovenous hemodiafiltration) 400mg IV q12h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which

combine dialysis with fluid removal.

 


Figure 1.  Structure Activity Relationship of the Fluoroquinolones

 

Reproduced from reference (50), with permission.

Originally published in the Journal of Antimicrobial Chemotherapy1994;33(4): 685-706.


 

Figure 2.  Structure of the Fluoroquinolones

 

 

 

 

Figure 3. Time to Eradication Versus AUIC

 

Relationship between the day of bacterial eradication and AUIC values above 250 for cefmenoxime (●) and cirprofloxacin (■). At the same AUIC range above 250, ciprofloxacin eradicates bacteria earlier in therapy.


 

Figure 4.  Relationship Between Serum Concentrations and Selected MIC Values

 

Relationship between serum concentrations of ciprofloxacin and selected MIC values.  At each value of MIC, the AUIC and peak to MIC ratio is calculated. Values are based on a 750-mg dose given twice daily.