Fluoroquinolone antibiotics have been used for more than 40 years to treat a variety of infections from simple uncomplicated urinary tract infections to infections as severe as nosocomial-acquired pneumonia. Their availability both orally and intravenously, ease of dosing, favorable safety profile, and broad spectrum of activity have led to the pervasive use of these agents in both the community and institutions. Unfortunately, this widespread use has led to the development of resistance and subsequently, increased mortality. Resistance, specifically with Pseudomonas aeruginosa and Escherichia coli, as well as their association with the development of Clostridium difficile–associated diarrhea, has led many clinicians to question the use of fluoroquinolones in the critically ill. This article will review these issues related to the use of fluoroquinolones, in an effort to better define their role among institutionalized patients.
Hooper DCQuinolones. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone; 2000:404-423.
Linder JA, Huang ES, Steinman MA, Gonzales R., Stafford RSFluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med.2005;118:259-268.
5.
Oliphant CM, Green GMQuinolones: a comprehensive review. Am Fam Physician . 2002;65:455-464.
6.
Owens RC, Ambrose PGClinical use of the fluoroquinolones. Med Clin N Am . 2000;84:1447-1469.
7.
Saravolatz LD , Leggett J.Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones. Clin Infect Dis. 2003;37:1210-1215.
8.
Drlica K.Mechanism of fluoroquinolone action. Curr Opin Microbiol . 1999;2:504-508.
9.
Hooper DCMechanisms of fluoroquinolone resistance. Drug Resist Updat . 1999;2:38-55.
10.
Hooper DCEmerging mechanisms of fluoroquinolone resistance. Emerg Infect Dis. 2001;7:337-341.
11.
Martinez-Martinez L., Pascual A., Jacoby GAQuinolone resistance from a transferable plasmid . Lancet. 1998 ;351:797-799.
12.
Yamane K., Wachino J., Suzuki S., et al. New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother. 2007;51:3354-3360.
13.
Hopkins KL, Davies RH, Threlfall EJMechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments. Int J Antimicrob Agents. 2005 ;25: 358-373.
14.
Hsu DI, Okamato MP, Murthy R., Wong-Beringer A.Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes. J Antimicrob Chemother . 2005;55:535-541.
15.
Nseir S., Di Pompeo C., Soubrier S., et al. First-generation fluoroquinolone use and subsequent emergence of multiple drug-resistant bacteria in the intensive care unit. Crit Care Med. 2005;32:283-289.
16.
Levin PD, Fowler RA, Guest C., Sibbald WJ, Kiss A., Simor AERisk factors associated with resistance to ciprofloxacin in clinical bacterial isolates from intensive care unit patients. Infect Control Hosp Epidemiol. 2007;28:331-336.
17.
Neuhauser MM , Weinstein RA, Rydman R., Danzinger LH, Karam G., Quinn JPAntibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003;289:885-888.
18.
McCaig LF, Besser RE, Hughes JMAntimicrobial drug prescriptions in ambulatory care settings, United States, 1992-2000. Emerg Infect Dis . 2003;9:432-437.
19.
Lautenbach E., Metlay JP, Bilker WB, Edelstein PH, Fishman NOAssociation between fluoroquinolone resistance and mortality in Escherichia coli and Klebsiella pneumoniae infections: the role of inadequate empirical antimicrobial therapy . Clin Infect Dis. 2005;41:923-929.
20.
Gasink LB, Fishman LO, Weiner MG, Nachamkin I., Bilker WB, Lautenbach E.Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact. Am J Med.2006 ;119:526e19-526e25.
21.
Chen DK, McGeer A., de Azavedo JC, Low DE for the Canadian Bacterial Surveillance NetworkDecreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med.1999;341: 233-239.
22.
Davidson R. , Cavalcanti R., Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med. 2002;346:747-750.
23.
Ho PL, Tse WS, Tsang KW, et al. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin Infect Dis. 2001;32: 701-707.
24.
LaPlante KL , Rybak MJ, Tsuji B., Lodise TP, Kaatz GWFluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin . Antimicrob Agents Chemother . 2007;51:1315-1320.
25.
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.
26.
Polk RE, Johnson CK, McClish D., Wenzel RP, Edmond MBPredicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities . Clin Infect Dis. 2004;39:497-503.
27.
Richards MJ , Edwards JR, Culver DH, Gaynes RPNosocomial infections in medical intensive care units in the United States. Crit Care Med. 1999;27:887-892.
28.
Shorr AF, Susla GB, Kollef MHQuinolones for treatment of nosocomial pneumonia: a meta-analysis . Clin Infect Dis. 2005;40:S115-S122.
29.
Ray GT, Baxter R., DeLorenze G.Hospital-level rates of fluoroquinolone use and the risk of hospital-acquired infection with ciprofloxacin-nonsusceptible Pseudomonas aeruginosa. Clin Infect Dis. 2005;41:441-449.
30.
Orbritsch MD , Fish DN, MacLaren R., Jung R.National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002. Antimicrob Agents Chemother. 2004;48:4606-4610.
31.
Fridkin SK, Hill HA, Volkova NV, et al. Temporal changes in prevalence of antimicrobial resistance in 23 US Hospitals. Emerg Infect Dis. 2002;8:697-701.
32.
Tigecycline Evaluation Surveillance Trial. Available at: http://www.testsurveillance.com. Accessed December 6, 2007.
33.
Antimicrobial Resistance Management (ARM) program. Available at: http://www.armprogram.com. Accessed December 6, 2007.
34.
Karlowsky JA , Jones ME, Thornsberry C., Evangelista AT, Yee YC, Sahm DFStable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001-2003 tracking resistance in the United States today (TRUST) surveillance studies. Clin Infect Dis. 2005;40:S89-S98.
35.
Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003;37: 997-1005.
36.
Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004;39:885-910.
37.
Fihn SDAcute uncomplicated urinary tract infection in women. N Engl J Med. 2003;349:259-266.
38.
Rhomberg PR , Deshpande LM, Kirby JT, Jones RNActivity of meropenem as serine carbapenemases evolve in US medical centers: monitoring report from the MYSTIC program (2006). Diagn Microbiol Infect Dis. 2007 ;59:425-432.
39.
Jones RN, Pfaller MACiprofloxacin as broad-spectrum empiric therapy-are fluoroquinolones still viable monotherapeutic agents compared with beta-lactams: data from the MYSTIC Program (US)? Diagn Microbiol Infect Dis. 2002;42:213-215.
40.
Rodriguez-Baño J., Navarro MD, Romero L., et al. Bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis.2006;43:1407-1414.
41.
DeRyke CA, Kuti JL, Nicolau DPPharmacodynamic target attainment of six β-lactams and two fluoroquinolones against Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella species collected from United States Intensive Care Units in2004. Pharmacotherapy. 2007;27:333-342.
42.
Lister PD, Wolter DJLevofloxacin-imipenem combination prevents the emergence of resistance among clinical isolates of Pseudomonas aeruginosa. Clin Infect Dis . 2005;40:S105-S114.
43.
Shorr AF, Zadeikis N., Jackson WL, et al. Levofloxacin for the treatment of ventilator-associated pneumonia: a subgroup analysis from a randomized control trial. Clin Infect Dis. 2005;40:S123-S129.
44.
Blossom D., McDonald C.The challenges posed by reemerging Clostridium difficile infection . Clin Infect Dis. 2007;45:222-227.
45.
Thomas C., Stevenson M., Riley TVAntibiotics and hospital-acquired Clostridium difficile-associated diarrhea: a systematic review. J Antimicrob Chemother. 2003;51: 1339-1350.
46.
McDonald LC , Owings M., Jernigan D.Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006;23: 409-415.
47.
Gerding DNClindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis. 2004;38:646-648.
48.
Stein GE, Goldstein EJC.Fluoroquinolones and anaerobes. Clin Infect Dis. 2006;42:1598-1607.
49.
Spencer RCThe role of antimicrobial agents in the etiology of Clostridium difficile-associated disease. J Antimicrob Chemother. 1998;41:21-27.
50.
Gaynes R., Rimland D., Killum E., et al. Outbreak of Clostridium difficile infection in a long-term care facility: association with gatifloxacin use. Clin Infect Dis . 2004;38:640-645.
51.
Adams DA, Riggs MM, Donskey CJEffect of fluoroquinolone treatment on growth of and toxin production by epidemic and nonepidemic Clostridium difficile strains in the fecal contents of mice . Antimicrob Agents Chemother. 2007 ;51:2674-2678.
52.
McDonald LC , Killgore GE, Thompson A., et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005 ;353:2433-2441.
53.
Pepin J., Valiquette L., Alary ME, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ. 2004;171:466-472.
54.
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.
55.
Loo VG, Poirier L., Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353:2442-2449.
56.
Muto CA, Pokrywka M., Shutt K., et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005;26:273-280.
57.
McCusker ME , Harris AD, Perencevich E., Roghmann M.Fluoroquinolone use and Clostridium difficile-associated diarrhea. Emerg Infect Dis. 2003;9:730-733.
58.
Bourgault AM , Lamothe F., Loo VG, Poirier L.In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Quebec, Canada. Antimicrob Agents Chemother. 2006;50: 3473-3475.
