Chapter 25 : Adverse Effects

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Adverse Effects, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817817/9781555812317_Chap25-1.gif /docserver/preview/fulltext/10.1128/9781555817817/9781555812317_Chap25-2.gif


The fluoroquinolone class of agents has been plagued by a number of compounds that have undergone an extensive clinical evaluation and have achieved distinctive clinical results but were not introduced into the market because of unacceptable safety and tolerability. Sparfloxacin use was severely curtailed because of associated phototoxic effects and cardiotoxicity. Grepafloxacin was also removed from the market shortly after its introduction because of cardiotoxicity. Fluoroquinolones presently marketed, or those that are in the final stage of clinical trials, seem to be well tolerated, with average adverse event rates of 20 to 30% for most compounds that are not significantly different from those of cephalosporins. Bone marrow cells are the most rapidly dividing eukaryotic cells, and therefore, considered most susceptible to agents affecting DNA synthesis. Ciprofloxacin, enoxacin, levofloxacin, nalidixic acid, ofloxacin, pipemidic acid, and N1-cyclopropyl quinolones were capable of inducing micronuclei in in vitro assays of mouse bone marrow cells. Allergic interstitial nephritis (AIN) is thought to be the most common form of fluoroquinolone nephrotoxicity and is attributed to a type III hypersensitivity reaction. Fluoroquinolones are usually well tolerated with a minimum of serious adverse effects, and renal toxicity is uncommon. Desensitization to ciprofloxacin in a patient with a prior history of maculopapular rash was attempted successfully. In summary, antibiotic treatment, in general, can lead to vaginitis induced by Candida in a frequency varying between 0.5 and 8%.

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Quinolone structure-side effect relationships. Modified from reference with permission.

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Al-Hedaithy, M. A.,, and A. M., Noreddin. 1996. Hypersensitivity an aphylactoid reaction to pefloxacin in a patient with AIDS. Ann. Pharmacother. 30:612614.
2. Asperilla, M. O.,, and R. A. Smego, Jr. 1989. Eosinophilic meningitis associated with ciprofloxacin. Am. J. Med. 87:589590.
3. Baden, L. R.,, G. Horowitz,, H. Jacoby,, and G. M. Eliopoulos. 2001. Quinolones and false-positive urine screening for opiates by immunoassay technology. JAMA 286:31153119.
4. Bailly, S.,, M. Fay,, B. Ferrua,, and M. A. Gougerot-Pocidalo. 1991. Ciprofloxacin treatnment in vivo increases the ex-vivo capacity of lipopolysaccharide-stimulated human monocytes to produce IL-1, IL-6 and tumor necrosis factor-alpha. Clin. Exp. Immunol. 85:331334.
5. Ball, P.,, L. Mandell,, Y. Niki,, and G. Tillotson. 1999. Comparative tolerability of the newer fluoroquinolones antibacterials. Drug Saf. 21:407421.
6. Ball, P. 2001. Future of the quinolones. Semin. Respir. Infect. 16:215224.
7. Ball, P. 1986. Ciprofloxacin: an overview of adverse experiences. J. Antimicrob. Chemother. 18(Suppl. D):187193.
8. Ball, P.,, and G. S. Tillotson. 1995. Tolerability of fluoroquinolone antibiotics: past, present and future. Drug Saf. 13:343358.
9. Barman Balfour, J. A.,, and H. M. Lamb. 2000 Moxifloxacin. Drugs 59:115139.
10. Berkovitch, M.,, A. Pastuszak,, M. Gazarian,, M. Lewis,, and G. Koren. 1994. Safety of new quinolones in pregnancy. Obst. Gynecol. 84:535538.
11. Bircher A. J.,, and M. Rutishauser. 1997. Oral "desensitization" of maculopapular exanthema from ciprofloxacin. Allergy 52:12461248.
12. Blank, M.,, J . George,, P. Fishman,. Y. Levy, V. Toder,, S. Savyon,, V. Barak,, T. Koike,, and Y. Schoenfeld. 1998. Ciprofloxacin immunomodulation of experimental antiphospholipid syndrome associated with elevation of interleukin-3 and granulocyte-macrophage-colony-stimulating factor expression. Arthritis Rheum. 41:224232.
13. Blum, M. D.,, D. J. Graham,, and C. A McCloskey. 1994. Temafloxacin syndrome: review of 95 cases. Clin. Infect. Dis. 18:946950.
14. Bomford, J. A.L.,, J. C. Ledger,, B. J. O'Keefe,, and C. Reiter. 1993. Ciprofloxacin use during pregnancy. Drugs 45(Suppl. 3):461462.
15. Breban, M.,, C. Fournier,, M. A. Gougerot-Pocidalo,, M. Muffat-Joly,, and J. J. Pocidalo. 1992. Protective effects of ciprofloxacin against type II collagen induced arthritis in rats. J. Rheumatol. 19:216222.
16. Breen, J .,, K. Skuba,, and D. Grasela. 1999. Safety and tolerability of gatifloxacin, an advanced-generation 8-methoxy fluoroquinolone. J. Respir. Dis. 20:7076.
17. Broide, E.,, B. Douer,, N. Shaked,, A. Yellin,, Y. Liberman,, N. Rosen,, S. Segev,, and E. Rubinstein. 1992. Effect of short term therapy with ciprofloxacin, ceftriaxone and placebo on human peripheral WBC and marrow derived granulocytes, macrophages progenitor cells (CFU-GM). Eur. J. Haematol. 48:276277.
18. Burke, P.,, and S. R. Burne. 2000. Allergy associated with ciprofloxacin Br. Med. J. 320:679.
19. Campoli-Richards, D. M.,, J . P. Monk,, A. Price,, P. Benfield,, P. A. Todd,, and A. Ward. 1988. Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 35:373447.
20.Centers for Disease Control and Prevention Update. 2001. Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy. Morb. Mortal. Wkly. Rep. 50:909919.
21. Chen, H. J. L.,, K. J. Bloch,, and J. A. Mclean. 2000. Acute eosinophilic hepatitis from trovafloxacin. N. Engl. J. Med. 342:359360.
22. Chodosh, S.,, C.A. De Abate,, D. Havestode,, L. Aneiro,, and D. Church. 2000. Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. Respir. Med. 94:1827.
23. Christ, W.,, T. Lehnert,, and B. Ulbrich. 1988. Specific toxicologic aspects of the quinolones. Rev. Infect. Dis. 10(Suppl.):S141S146.
24. Clutterbuck, D. J.,, and A. McMillan. 1997. Anaphylactoid reaction to ciprofloxacin. Int. J. STD AIDS 8:707708.
25. Coleman, C. I.,, J. V. Spencer,, J. O Chung,, and P. Reddy. 2002. Possible gatifloxacin induced fulminant hepatic failure. Ann. Pharmacother 36:11621167.
26. Corrado, M. L.,, W. E. Struble,, C. Peter,, V. Hoagland,, and J . Sabbaj. 1987. Norfloxacin: review of safety studies. Am. J. Med. 82(Suppl. 6A):129S133S.
27. Cukierski, M. A.,, S. Prahalada,, A. G. Zacchei,, C. P. Peter,, J . D. Todgers,, D. L. Hess,, M. J. Cukierski,, A. F. Trantal,, T. Nyland,, and R. T. Robertson. 1989. Embryotoxicity studies of norfloxacin in cynomolgus monkeys. I. Teratology studies and norfloxacin plasma concentration in pregnant and nonpregnant monkeys. Teratology 39:3952.
28. Davila, I.,, M. L. Diez,, S. Quirce,, J. Fraj,, B. De La Hoz,, and M. Lazaro. 1993. Cross reactivity between quinolones. Report of three cases. Allergy 48:388390.
29. Davis, R.,, and H. M. Bryson. 1994. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs 47:677700.
30. Davis, H.,, E. McGoodwin,, T. Greene,, and T. Reed. 1989. Anaphylactoid reactions reported after treatment with ciprofloxacin. Ann. Intern. Med. 111:1041.
31. De Simone, C.,, L. Baldinelli,, M. Ferrazzi,, S. De Santis,, L. Pugnaloni,, and F. Sorice. 1986. Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and pipemidic acid on human gamma-interferon production and blastogenesis. J. Antimicrob. Agents Chemother. 17:811814.
32. Dharnidharka, V. R.,, K. Nadeau.,, C. L. Cannon.,, H. W. Harris.,, and S. Rosen. 1995. Ciprofloxacin overdose: acute renal failure with prominent apoptotic changes. Am. J. Kidney Dis. 26:516519.
33. Domagala, J. M. 1994. Structure-activity and structure-sideeffect relationships for the quinolone antibacterials. J. Antimicrob. Chemother. 33:685706.
34. Erdem, G.,, M. A. Staat,, B. L. Connelly,, and A. Assa'ad. 1999. Anaphylactic reaction to ciprofloxacin in a toddler: successful desensitization. Pediatr. Infect. Dis. J. 18:563564.
35. Fernandez-Rivas, M. 1997. Fixed drug eruption (FDE) caused by norfloxacin. Allergy 52:477478.
36. Ford, C. D.,, W. Reiley,, J. Wood,, D. C. Classen,, and J. P. Burke. 1998. Oral antimicrobial prophylaxis in bone marrow transplant recipients: randomized trial of ciprofloxacin versus ciprofloxacin-vancomycin. Antimicrob. Agents Chemother. 42:14021408.
37. Forsgren, A.,, S. F. Sclossman,, and T. F. Tedder. 1987. 4- Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro. Antimicrob. Agents Chemother. 31:768773.
38. Freifield, A.,, D. Marchigiani,, T. Walsh,, S. Chanock,, L. Lewis,, J . Hiemenz,, S. Hiemenz,, J. E.,. Hicks,, C. Gill,, S. M. Steinberg,, and P. A. Pizzo. 1999. A double blind comparison of empirical oral and intravenous antibiotic therapy for lowrisk febrile patients with neutropenia during cancer chemotherapy. N. Engl. J. Med. 341:305311.
39. Friedman, J. M.,, and J.E. Polifka. Teratogenic Effects of Drugs: a Resource for Clinicians (TERIS), p. 149195. Johns Hopkins University Press, Baltimore, Md.
40. Galley, H. F.,, J. K. Dhillon,, R. L. Patterson,, and N. R. Webster. 2000. Effect of ciprofloxacin on the activation of the transcription factors, nuclear factor kappaB, activator protein-1 and nuclear-factor-IL-6 and interleukin-6 and interleukin-8 mRNA expression in human endothelial cell line. Clin. Sci. (Lond.) 99:405410.
41. Gea-Banacloche, J. C.,, and D. D. Metcalfe. 1996. Ciprofloxacin desensitization. J. Allergy Clin. Immunol. 97:14261427.
42. Geddes, A.,, M. Thaler,, S. Schonwald,, M. Harkonen,, F. Jacobs,, and I. Nowotny. 1999. Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial. J. Antimicrob. Chemother. 44:799810.
43. Godin, M.,, T. Ducastelle,., E. Bercoff,, D. Dubois,, J. P. Fillastre,, and J. Bouneille. 1984. Renal failure and quinolone. Nephron 37:70.
44. Gollapudi, S. V.,, S. K. Chuah,, T. Harvey,, H. D. Thadepalli,, and H. Thadepalli. 1993. In vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. Antimicrob. Agents Chemother. 37:17111712.
45. Gonzalez, J.P.,, and J. M. Henwood. 1989. Pefloxacin: a review of its antibacterial activity, pharmacokinetic properties, and therapeutic uses. Drugs 37:628686.
46. Hahn, T.,, Y. Barak,, E. Leibovitch,, L. Malach,, O. Dagan,, and E. Rubinstein. 1991. Ciprofloxacin inhibits human hematopoietic cell growth synergism with tumor necrosis factor and interferon. Exp. Hematol. 19:157160.
47. Halkin, H. 1988. Adverse effects of the fluoroquinolones. Rev. Infect. Dis. 10(Suppl. 1):258261.
48. Hooper, D. C.,, and J. S. Wolfson,. 1993. Adverse effects, p. 489512. In D. C. Hooper, and J. S. Wolfson (ed.), Quinolone Antimicrobial Agents , 2nd ed. American Society for Microbiology, Washington, D.C..
49. Hootkins, R.,, A. Z. Fenves,, and M. K. Stephens. 1989 Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature. Clin. Nephrol. 32:7578.
50. Hughes, W. T.,, D. Armstrong,, G. P. Bodey,, A. E. Brown,, J . E., Edwards,, R. Feld,, P. Pizzo,, K. V. I. Rolston,, J . L. Shenep,, and L. S. Young. 1997. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fevers. Clin. Infect. Dis. 25:551573.
51. Hummler, H.,, W. F. Richter,, and A. G. Hendrickx. 1993. Developmental toxicity of fleroxacin and comparative pharmacokinetics of four fluoroquinolones in the cynomolgus macaque (Macaca fascicularis). Toxicol. Appl. Pharmacol. 122:3445.
52. Iannini, P. B.,, R. Rubin,, C. Reiter,, and G. Tillotson. 2001. Reassuring safety profile of moxifloxacin. Clin. Infect. Dis. 32:11121114.
53. Inglesby, T. V.,, D. A. Henderson,, J . G. Bartlett,, M. S. Ascher,, E. Eitzen,, A. M. Friedlander,, J . Hauer,, J . McDade,, M. T. Osterholm,, T. O'Toole,, G. Parker,, T. M. Perl,, P. K. Russell, and, K. Tonat for the Working Group on Civilian Biodefense. 1999. Anthrax as a biological weapon: medical and public health management. JAMA 281:17351745.
54. Itoh, S.,, M. Miura,, and H. Shimada. 1998. Lack of mutagenicity of levofloxacin in lacZ transgenic mice. Mutagenesisl3:5155.
55. Jungst, G.,, and R. Mohr. 1988. Overview of post-marketing experience with ofloxacin in Germany. J. Antimicrob. Chemother. 22:(Suppl. C):167175.
56. Kaloyanides, G. J . 1994. Antibiotic-related nephrotoxicity. Nephrol. Dial. Transplant. 9(Suppl. 4):130134.
57. Kern, W.,, and E. Kurrle. 1991. Ofloxacin versus trimethoprim- sulfamethoxazole for prevention of infection in patients with acute leukemia and granulocytopenia. Infection 19:7380.
58. Kern, W. V.,, A. Cometta,, R. De Bock,, J . Lamgenakken,, M. Paesmans,, H. Gaya. 1999. Oral versus intravenous empirical therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. N. Engl. J. Med. 341:312318.
59. Khan, A. A.,, T. R. Slifer,, F. G. Araujo,, Y. Suzuki,, and J . S. Remington. 2000. Protection against lipopolysaccharideinduced death by fluoroquinolones. Antimicrob. Agents Chemother. 44:31693173.
60. Kimyai-Asadi, A.,, A. Usman,, and H. C. Noiusari. 2000. Ciprofloxacin-induced bullous pemphigoid. J. Am. Acad. Dermatol. 42(5 Pt 1):847.
61. Kletter, Y .,, I. Riklis,, and I. Shalit,, I. Fabian. 1991 Enhanced repopulation of murine hematopoietic organs in sublethally irradiated mice after treatment with ciprofloxacin. Blood 78:16851691.
62. Lien, Y. H.,, R. Hansen,, W. F. Kern,, J . Bagert,, R. B. Nagle,, and M. Ko,, and M. S. Siskind. 1993. Ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. Am. J. Kidney Dis. 22:598602.
63. Lipsky, B. A.,, and C. A. Baker. 1999. Fluoroquinolone toxicity profiles: a review focusing on newer agents Clin. Infect. Dis. 28:352364.
64. Livasy, C. A.,, and A. M. Kaplan. 1997. Ciprofloxacininduced toxic epidermal necrolysis: a case report and a review. Dermatology 195:173175.
65. Lo, W. K.,, K. V. I. Rolston,, E. B. Rubenstein,, and G. P. Bodey. 1993. Ciprofloxacin induced nephrotoxicity in patients with cancer. Arch. Intern. Med. 153:12581262.
66. Loebstein, R.,, A. Addis,, E. Ho,, R. Andreou,, S. Sage,, A. E. Donnenfeld,, B. Schick,, M. Bonati,, M. Moretti,, A. Lalkin,, A. Pastuszak,, and G. Keren. 1998. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob. Agents Chemother. 42:13361339.
67. Lomaestro, B. M. 2000. Fluoroquinolone-induced renal failure. Drug Saf. 22:479485.
68. Mandell, L. A.,, P. Ball,, and G. Tillotson. 2001. Antimicrobial safety and tolerability: differences and dilemmas. Clin. Infect. Dis. 32(Suppl. 1):S72S79.
69. Massoomi, T.,, H. G Mathews,, and C. J . Destache. 1993. Effect of seven fluoroquinolones on the detemination of serum creatinine by the picric acid and enzymatic methods. Ann. Pharmacother. 27:586588.
70. Mitropoulos, F. A,, P. B. Angood,, and R. Rabinovici. 2001. Trovafloxacin-associated leukopenia. Ann. Pharmacother. 35:4144.
71. Montey, G.,, Y. Goueffon,, and F. Roquet. 1984. Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys, and humans. Antimicrob. Agents Chemother. 25:463472.
72. Naldi, L.,, A. Conforti,, M. Venegoni,, M. G. Troncon,, A. Caputi,, E. Ghiotto,, A. Cocci,, U. Moretti,, G. Velo,, and R. Leone. 1999. Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions. Br. J. Clin. Pharmacol. 48:839846.
73. Nicholson, S. C.,, C. D. Webb,, and R. C. Moellering. 2002. Antimicrobial-associated acute hepatitis. Pharmacotherapy 22:794796.
74. Nishijima, S.,, and M. Nakagawa. 1997. Fixed drug eruption caused by tosufloxacin tosillate. J. Int. Med. Res. 25:359363.
75. Nordmann, P.,, M. Diez-Ibanez,, M. Chessebeuf-Padieu,, B. Luu,, G. Mack,, and M. Mersel. 1999. Toxic effects of 7 0- hydroxycholesterol on rat liver cells primary cultures, epithelial lines, and co-cultures. Cell Biol. Toxicol. 5:261270.
76. Norrby, S. R.,, and P. S. Lietman. 1993. Safety and tolerability of fluoroquinolones. Drugs 45(Suppl. 3):5964.
77. Pace, J . L.,, and P. Gatt. 1989. Fatal vasculitis associated with ofloxacin. Br. Med. J. 299:658.
78. Paily, R. 2000. Quinolone drug rash in a patient with infectious mononucleosis. J. Dermatol. 27:405406.
79. Pallavacini, F.,, A. Antinori,, G. Frederico,, M. Funtoni,, and P. Neruo. 1989. Influence of two quinolones, ofloxacin and pefloxacin, on human myelopoesis in vitro. Antimicrob. Agents Chemother. 33:122123.
80. Perry, C. M.,, D. Ormrod,, M. Hurst,, and S. V. Onrust. 2001. Gatifloxacin: a review of its use in the management of bacterial infections. Drugs 61:137.
81. Pessina, A.,, M. G. Neri,, E. Muschiato,, E. Mineo,, and G. Cocuzza. 1989. Effect of fluoroquinolones on the in-vitro proliferation of myeloid precursor cells. J. Antimicrob. Chemother. 24:203208.
82. Reano, M.,, R. Vives,, J . Rodriguez,, P. Daroca,, G. Canto,, and J . Fernandez. 1997. Ciprofloxacin-induced vasculitis. Allergy 52:599600.
83. Remuzon, P.,, D. Bouzard,, C. Guiol,, and J . Jacquet. 1992. Fluoronaphtypyridines as antibacterial agents. 6. Synthesis and structure activity relationship of new chiral 7-(l-,3-,4-, and 6- methyl-2,5-diazabicyclo[2.2.1]-heptan-2-yl]-l-(l,l dimethyl)- 6-fluoro-l,4-dihydro-oxo-l,8-naphthyridine-3-carboxylix acid. Influence of the configuration on blood pressure in dogs: a quinolone-class effect. J. Med. Chem. 35:28982899.
84. Riesbeck, K. 2002. Immunomodulating activity of quinolones. Rev. J. Chemother. 14:312.
85. Riesbeck, K.,, A. Forsgren,, A. Henriksson,, and A. Bredberg. 1998. Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes. Antimicrob. Agents Chemother. 42:19231930.
86. Riesbeck, K.,, and A. Forsgren. 1994. Increased 11-2 transcription in murine lymphocyte by ciprofloxacin. Immunopharmacology 27:155164.
87. Riesbeck, K.,, and A. Forsgren. 1998. Commentary on ciprofloxacin superinduction of 11-2 synthesis and thymidine uptake. Transplantation 65:12821283.
88. Riesbeck, K.,, H. Schatz,, O. Ostraat,, G. Tufveson,, and H. Ekberg. 1995. Enhancement of the immuno-suppressive effect of cyclosporin A by ciprofloxacin in a rat cardiac transplantation model. Transplant. Int. 8:96102.
89. Rubinstein, E. 1996. Safety profile of sparfloxacin in the treatment of respiratory tract infections. J. Antimicrob. Chemother. 37:(Suppl. A):145160.
90. Rubinstein, E.,, P. Potgieter,, P. Davey,, and S. R. Norrby. 1994. The use of fluoroquinolones in neutropenic patients—analysis of adverse effects. J. Antimicrob. Chemother. 34:719.
91. Salon, E. J.,, M. A. Newbrough,, C. A. Albarracin,, and J. E. Hernandez. 1997. Anaphylactoid reaction to ciprofloxacin versus toxic shock syndrome. Ann. Pharmacother. 1:119120.
92. Sangen, Y.,, A. Kawada,, M. Asai,, Y. Aragane,, T. Yudate,, and T. Tezuka. 2000. Fixed drug eruption induced by tosufloxacin tosilate. Contact Dermatitis 42:285.
93. Sanders, W. E., Jr. 1988. Efficacy, safety and potential economic benefits of oral ciprofloxacin in the treatment of infections. Rev. Infect. Dis. 10:528543.
94. Savion, S.,, M. Lank,, J. Shepshelovich,, P. Fishman,, Y. Schoenfeld,, and V. Toder. 2000. Ciprofloxacin affects pregnancy loss in CBA/JxDBA/2J mice possibly via elevation of interleukin-3 and granulocyte-macrophage-colony-stimulating factor production. Am. J. Reprod. Immunol. 44:293298.
95. Schaefer, C.,, E. Amoura-Elefant,, T. Vial,, A. Ornoy,, H. Garbis,, E. Robert,, E. Rodriguez-Pinilla,, T. Pexeider,, N. Prapas,, and P. Merlob. 1996. Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS). Eur. J. Obst. Gynecol. 69:8389.
96.. Shalit, I.,, Y. Kletter,, K. Weiss,, T. Grass,, and I. Fabian. 1997. Enhanced hematopoiesis in sublethally irradiated mice treated with various quinolones. Eur. J. Haematol. 58:9298.
97. Shalit, I.,, Y. Kletter,, D. Halperin,, D. Waldman,, E. Vasserman,, A. Nagler,, and I. Fabian. 2001. Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G-CSF in a murine model of cyclophosphamide-induced leukopenia. Eur. J. Haematol. 66:287296.
98. Shimada, H.,, and S. Itoh. 1996. Effects of new quinolone antibacterial agents on mammalian chromosomes. J. Toxicol. Environ. Health 47:115123.
99. Smythe, M. A.,, and D. M. Cappelletty. 2000. Anaphylactoid reaction to levofloxacin. Pharmacotherapy 20:15201523.
100. Somekh, E.,, B. Lew,, E. Schwartz,, A. Barzilai,, and E. Rubinstein. 1989. The effect of ciprofloxacin and pefloxacin on bone marrow engraftment in the spleen of mice. J. Antimicrob. Chemother. 19:781790.
101. Somekh, E.,, S. West,, A. Barzilai,, and E. Rubinstein. 1989. The lack of long term suppressive effect of ciprofloxacin on murine bone marrow. J. Antimicrob. Chemother. 24:209213.
102. Stahlmann, R. 1990. Safety profile of the quinolones. J. Antimicrob. Chemother. 26(Suppl. D):3134.
103. Stahlmann R.,, and H. Lode,. 2000. Safety overview: Toxicity, adverse effects, and drug interactions, p. 370416. In V. T. Andriole (ed.), The Quinolones, 2nd ed. Academic Press, Inc., New York. N.Y..
104. Stahlmann, R.,, and R. Schwabe. 1997. Safety profile of grepafloxacin compared with other fluoroquinolones. J. Antimicrob. Chemother. 40(Suppl. A):8392.
105. Takayama, S.,, M. Hirohashi,, M. Kato,, and H. Shimada. 1995. Toxicity of quinolone antimicrobial agents. J. Toxicol. Environ. Health 45:145.
106. Takayama, S.,, T. Watanabe,, Y. Akiyama,, K. Ohura,, S. Harada,, K. Matsuhashi,, K. Mochida,, and N. Yamashita. 1986. Reproductive toxicity of ofloxacin. Arzneim.-Forsch. 36:12441248.
107. Tarantal, A. F.,, S. B. Lehrer,, B. L. Lasley,, and A. G. Hendrickx. 1990. Developmental toxicity of temafloxacin hydrochloride in the long-tailed macquaque (Maccaca fascicularis). Teratology 42:233242.
108.U.S. Food and Drug Administration. 1999. Public Health Advisory. Trovan (Trovafloxacin/Alatrofloxacin Mesylate. 9 June 1999) . U.S. Food and Drug Administration, Washington, D.C..
109. Wagstaff, A. J .,, and J. A. Balfour. 1997. Grepafloxacin. Drugs 53:817824.
110. Wang, C. X .,, J. Sabbaj,, M. Corrado,, and J. Hoagland. 1986. Worldwide clinical experience with norfloxacin: efficacy and safety. Scand. J. Infect. Dis. Suppl. 28:8189.
111. Watanabe, T.,, K. Fujikawa,, S. Harada,, K. Ohura,, T. Sasaki,, and S. Takayama. 1992. Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits. Arzneim.-Forsch. 43:374377.
112. Wolfson, J . S. 1989. Quinolone antimicrobial agents: adverse effects and bacterial resistance. Eur. J. Clin. Microb. Infect. Dis. 8:10801092.
113. Wolfson, J . S.,, and D. C. Hooper. 1991. Overview of fluoroquinolone safety. Am. J. Med. 91(Suppl. 6A):153161.
114. Yerasi, A. B.,, and M. D. Oertal. 1996. Ciprofloxacin-induced toxic epidermal necrolysis. Ann. Pharmacother. 30:297.
115. Zakari, S. M.,, H. Meyer,, G. Meinhardt,, W. Reinisch,, K. Scrattbauer,, M. Knoefler,, and L. H. Block. 2000. Effects of trovafloxacin on the IL-1 dependent activation of E-selection in human endothelial cells in vitro. Immunopharmacology 48:2734.


Generic image for table
Table 1

Serious fluoroquinolone-associated adverse events leading to drug withdrawals, severe restrictions, or suspensions from the market

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Generic image for table
Table 2

Overall incidence of fluoroquinolone-associated adverse events

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Generic image for table
Table 3

Overall incidence of adverse events associated with fluoroquinolones (U.S./European data)

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Generic image for table
Table 4

Drug discontinuation rate of new fluoroquinolones due to adverse events

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Generic image for table
Table 5

Post-launch adverse reaction spontaneous reporting to the FDA (levofloxacin/trovafloxacin)

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25
Generic image for table
Table 6

Skin rashes (%) associated with fluoroquinolones

Citation: Lode H, Rubinstein E. 2003. Adverse Effects, p 407-419. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch25

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error