search text   Advanced Search

This Article Abstract Full Text (PDF) P3Rs: Submit a response P3Rs: View responses Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Related Collections Therapeutics & Toxicology

The Use of Systemic Fluoroquinolones

	ABSTRACT

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
The only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed by the US Food and Drug Administration for use in patients younger than 18 years are complicated urinary tract infections, pyelonephritis, and postexposure treatment for inhalation anthrax. Nonetheless, approximately 520 000 prescriptions for fluoroquinolones were written in the United States for patients younger than 18 years in 2002; 13 800 were written for infants and children 2 to 6 years of age, and 2750 were written for infants younger than 2 years. Clinical trials of fluoroquinolones in pediatric patients with various diagnoses have been published and are reviewed. Fluoroquinolones cause arthrotoxicity in juvenile animals and have been associated with reversible musculoskeletal events in both children and adults. Other adverse events associated with fluoroquinolones include central nervous system disorders, photosensitivity, disorders of glucose homeostasis, prolongation of QT interval with rare cases of torsade de pointes (often lethal ventricular arrhythmia in patients with long QT syndrome), hepatic dysfunction, and rashes. The increased use of fluoroquinolones in adults has resulted in increased bacterial resistance to this class of antibacterial agents. This report provides specific guidelines for the systemic use of fluoroquinolones in children. Fluoroquinolone use should be restricted to situations in which there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria or to provide oral therapy when parenteral therapy is not feasible and no other effective oral agent is available.

Key Words: fluoroquinolones • ciprofloxacin • antibacterial agents • antimicrobial agents • antibiotics

Abbreviations: FDA—Food and Drug Administration • CF—cystic fibrosis • MIC—minimum inhibitory concentration

	BACKGROUND

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Nalidixic acid was the first quinolone antibacterial agent licensed for use in the United States. Since introduction of nalidixic acid in the 1960s, subsequent generations of fluoroquinolones have been licensed by the US Food and Drug Administration (FDA). Fluorination of quinolone compounds resulted in the introduction of norfloxacin in 1986 and ciprofloxacin in 1987, followed by other second-generation fluoroquinolones. Additional modifications resulted in third- and fourth-generation fluoroquinolones (Table 1). Some fluoroquinolones are no longer available, and others are of limited use clinically. Currently, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin are the most widely used fluoroquinolones.

Numerous reports describe use of fluoroquinolones to treat infections in children. Reported uses include treatment of exacerbations of bronchopulmonary disease in children with cystic fibrosis (CF) who have colonization with Pseudomonas aeruginosa, complicated urinary tract infections, chronic suppurative otitis media associated with P aeruginosa, osteochondritis attributable to P aeruginosa, shigellosis, invasive salmonellosis, and Campylobacter jejuni infections. In recent years, use has also included prophylaxis during periods of neutropenia; empiric therapy in febrile, neutropenic children with cancer; treatment of patients with multidrug-resistant Gram-negative bacillary septicemia or meningitis; and combination use with other agents to treat multidrug-resistant mycobacterial disease.¹

Reports on use of fluoroquinolones in children include retrospective studies, studies without control groups, and studies that include small numbers of children in selected populations. In these reports, arthropathy (as observed in animals) was not noted, or if a musculoskeletal event did occur, it was reversible.

	STATEMENT OF PROBLEM OF RESISTANCE TO FLUOROQUINOLONES

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Despite the fact that postexposure treatment for inhalation anthrax was the only licensed indication for use of systemic fluoroquinolones in patients younger than 18 years before 2004, there were approximately 520 000 prescriptions written for children and adolescents younger than 18 years in the United States in 2002. Approximately 13 800 of those prescriptions were written for children 2 to 6 years of age, and 2750 were written for infants younger than 2 years.

The increased use of fluoroquinolones in all age groups is resulting in a corresponding increase in bacterial resistance to fluoroquinolones. One study in adult patients with CF demonstrated that the proportion of susceptible P aeruginosa isolates decreased from 100% to 45% after 14 days of treatment.² Studies from many countries have reported resistance to fluoroquinolones among C jejuni, Shigella species, Salmonella species, and shiga toxin-producing Escherichia coli. In many geographic areas of the world, including the United States, resistance patterns have demonstrated a consistent increase over the course of time, with resistance occurring to several classes of antimicrobial agents, including fluoroquinolones.³

Fluoroquinolones also are being used for empirical and prophylactic treatment in patients receiving chemotherapy for cancer, which might further contribute to increased resistance to these agents. A total of 122 stool samples were collected from 25 adult patients with hematologic malignancies who were receiving prophylactic norfloxacin. Stool isolates of E coli were tested for susceptibility to norfloxacin.⁴ Two patients had fluoroquinolone-resistant E coli isolates before beginning norfloxacin treatment, and 8 (35%) of the remaining 23 patients had fluoroquinolone-resistant E coli isolated from stool samples after a mean of 10 days (range: 3–35 days) of norfloxacin prophylaxis.⁴ Enterococcal isolates resistant to ciprofloxacin and trovafloxacin were recovered from hospitalized children who had never received fluoroquinolones, which raised the possibility of nosocomial infections with fluoroquinolone-resistant bacteria.⁵

Resistance to fluoroquinolones among isolates of Streptococcus pneumoniae is increasing. Susceptibility testing of 5640 strains of S pneumoniae isolated during the 1997–1998 respiratory illness season from 377 hospitals throughout the United States showed only 0.3% of isolates to be resistant to ciprofloxacin (minimum inhibitory concentration [MIC]: 4 µg/mL).⁶ However, S pneumoniae isolated in the United States from January 1999 through August 2000 showed resistance to ciprofloxacin at 3%, levofloxacin at 0.5%, and gatifloxacin at 0.4%.⁷ In Canada, 2% of 1844 S pneumoniae isolates from patients of all ages in all provinces were resistant to ciprofloxacin during the 1997–1998 respiratory illness season.⁸ In Hong Kong during the second half of 1998, 12% of S pneumoniae isolates had an MIC greater than 2 µg/mL for ciprofloxacin, 6% had an MIC greater than 2 µg/mL for levofloxacin, and 2% had an MIC greater than 1 µg/mL for trovafloxacin.⁹ Although it has been suggested that introduction of moxifloxacin and gatifloxacin, which require both typoisomerase and gyrase production for resistance, will circumvent the growing resistance to fluoroquinolones, there is evidence that resistance to fluoroquinolones is essentially a class effect.¹⁰ Thus, increased use of fluoroquinolones can be anticipated to result in an increase in strains of S pneumoniae that are resistant to all fluoroquinolones. Resistance of P aeruginosa, Pseudomonas mirabilis, E coli, and other common hospital pathogens has increased consistently as fluoroquinolone use has increased.¹¹

	CLINICAL TRIALS IN PEDIATRIC PATIENTS

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Empirical Treatment for Fever in Neutropenic Children With Cancer
Several investigators have studied the empiric use of oral fluoroquinolones for outpatient treatment of children with cancer and fever and neutropenia who were considered at low risk of acquiring serious bacterial infections.¹² These studies have shown the potential benefits of such therapy and have reported few drug-related adverse events.

Treatment of Enteric Infections
Treatment of Salmonella typhi Infection
In a randomized, open-label trial, oral cefixime for 7 days was compared with oral ofloxacin for 5 days in 82 Vietnamese children with culture-proven typhoid fever.¹³ Treatment failures were significantly fewer, and days of fever, poor eating, and immobility were significantly shorter in the ofloxacin-treated patients. The study was undertaken because the incidence of infections with fluoroquinolone-resistant S typhi is increasing in Vietnam. The authors concluded that cefixime can provide a useful alternative treatment for uncomplicated typhoid fever in children but is less effective than ofloxacin.¹³

Treatment of Shigella dysenteriae Infection
The Zimbabwe, Bangladesh, South Africa (Zimbasa) Dysentery Study Group¹⁴ conducted a multicenter, randomized, double-blind controlled clinical trial in which 253 children between 1 and 12 years of age were randomly assigned to receive either a 3- or 5-day course of oral ciprofloxacin. S dysenteriae type I was isolated from stool specimens of 66 and 62 children in the short-course and standard-course groups, respectively. All isolates were susceptible to ciprofloxacin, and all children were microbiologically cured by day 5. Sixty-five percent of the children in the short-course group were cured clinically on day 5, compared with 69% in the standard-course group.¹⁴

Empirical Treatment of Bacterial Enteritis
Israeli children 6 months to 11 years of age with clinically defined invasive diarrhea were randomly assigned to receive either intramuscular ceftriaxone or oral ciprofloxacin in a double-blind controlled study.¹⁵ Enteric pathogens were isolated from 60% of the 201 children studied, and clinical cure or improvement was observed in 100% and 99% of the ciprofloxacin- and ceftriaxone-treated children, respectively. Although the study was carefully designed and executed, the empirical use of antibacterial agents to treat children with clinically defined invasive diarrhea is not indicated in most economically developed countries. The authors also did not address the potential for antibacterial treatment to increase the likelihood of hemolytic uremic syndrome in patients with invasive diarrhea caused by shiga toxin-producing E coli.¹⁶

Treatment of Francisella tularensis Infection
The outcomes of 12 Swedish children with ulceroglandular tularemia treated with oral ciprofloxacin were reported in a retrospective study; all of them recovered without complication.¹⁷ All isolates were susceptible to other antibacterial agents, and no comparison group was studied.

Treatment of Meningitis
An international multicenter trial compared the safety and efficacy of parenterally administered trovafloxacin with that of ceftriaxone with or without vancomycin for treatment of 203 evaluable patients with bacterial meningitis.¹⁸ No significant differences in clinical outcomes, including deaths, seizures, or severe sequelae, were detected at follow-up 5 to 7 weeks after treatment. Subsequently, trovafloxacin was associated with acute liver failure and death in adults. The FDA limited the indications for trovafloxacin to serious and life-threatening diseases, and the manufacturer decided to cease distribution of the drug. Thus, although a fluoroquinolone might have a role in the treatment of acute bacterial meningitis, no controlled trials in children have been reported using currently licensed drugs.

Treatment of Otitis Media
Two open-label, noncomparative trials of gatifloxacin to treat recurrent or nonresponsive acute otitis media have been published.¹⁹,²⁰ In a study conducted at a single center in Israel, 160 patients were enrolled, but 32 (20%) discontinued treatment prematurely, and an additional 14 (9%) were considered clinically unevaluable at the end of therapy.¹⁹ Of 114 patients clinically evaluable 12 to 14 days after commencing therapy, 90% were considered clinically cured. A multinational study enrolled 254 patients 6 months to 7 years of age with recurrent acute otitis media, treatment failure, or both.²⁰ Ultimately, 198 patients were evaluable clinically, and 58% had at least 1 pathogen isolated from their middle-ear fluid before treatment. The end-of-treatment clinical cure rate was 88%. Neither study used a precise clinical definition of acute otitis media, and neither enrolled a control group. The authors of both studies caution that fluoroquinolones should be used only in patients who do not respond to recommended antibacterial agents.

Arthropathy in Pediatric Patients
Despite statements to the contrary, fluoroquinolones have been associated with musculoskeletal adverse events in children. Pefloxacin was used extensively in France and was found to cause arthralgia/arthritis in children and adults. Ciprofloxacin pediatric labeling by the FDA includes data regarding musculoskeletal adverse events in pediatric patients 1 to 17 years of age who received ciprofloxacin or a control agent to treat complicated E coli urinary tract infections and pyelonephritis attributable to E coli. The rates of musculoskeletal adverse events occurring within 6 weeks of treatment were 9.3% (31 of 335) in patients receiving ciprofloxacin compared with 6.0% (21 of 349) in control patients.²¹ To date, most reported musculoskeletal events associated with fluoroquinolone use were of moderate intensity and were transient.²²,²³ Study of a large database did not demonstrate a difference in musculoskeletal toxicity between patients receiving ciprofloxacin or ofloxacin and azithromycin.²⁴ Fluoroquinolone-associated tendinopathy in adults is more likely to occur in older patients, patients receiving systemic corticosteroids, and patients with renal disease.²⁵

	RECOMMENDATIONS

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
The inappropriate use of fluoroquinolones in children and adults is likely to be associated with increasing bacterial resistance to these agents.

The use of a fluoroquinolone in a child or adolescent may be justified in special circumstances after careful assessment of the risks and benefits for the individual patient. Although there is no compelling evidence supporting the occurrence of sustained injury to developing joints in humans by a fluoroquinolone, the possibility that it occurs infrequently has not been excluded.

Circumstances in which fluoroquinolones may be useful include those in which (1) infection is caused by multidrug-resistant pathogens for which there is no safe and effective alternative and (2) parenteral therapy is not feasible and no other effective oral agent is available. Appropriate uses should be limited to the following:

• exposure to aerosolized Bacillus anthracis to decrease the incidence or progression of disease (FDA licensed) (evidence grade III; see Table 2);
  
• urinary tract infections caused by P aeruginosa or other multidrug-resistant, Gram-negative bacteria (FDA licensed for complicated E coli urinary tract infections and pyelonephritis attributable to E coli in patients 1–17 years of age) (evidence grade II-2);
  
• chronic suppurative otitis media or malignant otitis externa caused by P aeruginosa (evidence grade II-3);
  
• chronic or acute osteomyelitis or osteochondritis caused by P aeruginosa (not for prophylaxis of nail puncture wounds to the foot) (evidence grade III);
  
• exacerbation of pulmonary disease in patients with CF who have colonization with P aeruginosa and can be treated in an ambulatory setting (evidence grade II-2);
  
• mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones (evidence grade III);
  
• Gram-negative bacterial infections in immunocompromised hosts in which oral therapy is desired or resistance to alternative agents is present (evidence grade II-1);
  
• gastrointestinal tract infection caused by multidrug-resistant Shigella species, Salmonella species, Vibrio cholerae, or C jejuni (evidence grade II-2);
  
• documented bacterial septicemia or meningitis attributable to organisms with in vitro resistance to approved agents or in immunocompromised infants and children in whom parenteral therapy with other appropriate antimicrobial agents has failed (evidence grade III); and
  
• serious infections attributable to fluoroquinolone-susceptible pathogen(s) in children with life-threatening allergy to alternative agents (evidence grade III).
  

	COMMITTEE ON INFECTIOUS DISEASES, 2004–2005

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

Robert S. Baltimore, MD

Henry Bernstein, DO

Joseph A. Bocchini, Jr, MD

John S. Bradley, MD

Michael Brady, MD

Penelope H. Dennehy, MD

Robert W. Frenck, Jr, MD

David Kimberlin, MD

Sarah S. Long, MD

Julia A. McMillan, MD

Lorry G. Rubin, MD

	PAST COMMITTEE MEMBERS

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Carol J. Baker, MD

Caroline B. Hall, MD

H. Cody Meissner, MD

Margaret B. Rennels, MD

	LIAISONS

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Richard D. Clover, MD

American Academy of Family Physicians

Steven Cochi, MD

Centers for Disease Control and Prevention

Joanne Embree, MD

Canadian Paediatric Society

Marc A. Fischer, MD

Centers for Disease Control and Prevention

Benjamin Schwartz, MD

National Vaccine Program Office

Mamodikoe Makhene, MD

National Institutes of Health

Douglas Pratt, MD

Food and Drug Administration

Jeffrey R. Starke, MD

American Thoracic Society

Jack Swanson, MD

Practice Action Group

	EX OFFICIO

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Larry K. Pickering, MD

Red Book Editor

	CONSULTANT

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Edgar O. Ledbetter, MD

	STAFF

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Alison Siwek, MPH

	COMMITTEE ON INFECTIOUS DISEASES, 2003–2004

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Margaret B. Rennels, MD, Chairperson

H. Cody Meissner, MD, Vice Chairperson

Carol J. Baker, MD

Robert S. Baltimore, MD

Joseph A. Bocchini, Jr, MD

John S. Bradley, MD

Penelope H. Dennehy, MD

Robert W. Frenck, Jr, MD

Caroline B. Hall, MD

Sarah S. Long, MD

Julia A. McMillan, MD

^*Keith R. Powell, MD

Lorry G. Rubin, MD

Thomas N. Saari, MD

	LIAISONS

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Richard D. Clover, MD

American Academy of Family Physicians

Steven Cochi, MD

Centers for Disease Control and Prevention

Joanne Embree, MD

Canadian Paediatric Society

Marc Fischer, MD

Centers for Disease Control and Prevention

Bruce Gellin, MD, MPH

National Vaccine Program Office

Mamodikoe Makhene, MD

National Institutes of Health

Douglas Pratt, MD

Food and Drug Administration

Jeffrey R. Starke, MD

American Thoracic Society

	EX OFFICIO

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Larry K. Pickering

Red Book Editor

	STAFF

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 
Martha Cook, MS

	FOOTNOTES

 
All policy statements from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

^* Lead author

	REFERENCES

TOP ABSTRACT BACKGROUND STATEMENT OF PROBLEM OF... CLINICAL TRIALS IN PEDIATRIC... RECOMMENDATIONS COMMITTEE ON INFECTIOUS... PAST COMMITTEE MEMBERS LIAISONS EX OFFICIO CONSULTANT STAFF COMMITTEE ON INFECTIOUS... LIAISONS EX OFFICIO STAFF REFERENCES

 

1. Schaad UB, Abdus Salam M, Aujard Y, et al. Use of fluoroquinolones in pediatrics: consensus report of an International Society of Chemotherapy commission. Pediatr Infect Dis J. 1995;14 :1 –9[Medline]
2. Shalit I, Stutman HR, Marks MI, Chartrand SA, Hilman BC. Randomized study of two dosage regimens of ciprofloxacin for treating chronic bronchopulmonary infection in patients with cystic fibrosis. Am J Med. 1987;82(suppl 4A) :189 –195
3. Pickering LK. Antimicrobial resistance among enteric pathogens. Semin Pediatr Infect Dis. 2004;15 :71 –77[CrossRef][Medline]
4. Carratala J, Fernandez-Sevilla A, Tubau F, Dominguez MA, Gudiol F. Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis. Antimicrob Agents Chemother. 1996;40 :503 –505[Abstract]
5. McNeeley DF, Eckert SJ, Noel GJ. Antimicrobial-resistant enterococcal isolates from fluoroquinolone-naive children. Pediatr Infect Dis J. 2000;19 :675 –676[CrossRef][ISI][Medline]
6. Sahm DF, Peterson DE, Critchley IA, Thornsberry C. Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States. Antimicrob Agents Chemother. 2000;44 :2521 –2524[Abstract/Free Full Text]
7. White RL, Enzweiler KA, Friedrich LV, Wagner D, Hoban D, Bosso JA. Comparative activity of gatifloxacin and other antibiotics against 4009 clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000. Diagn Microbiol Infect Dis. 2002;43 :207 –217[CrossRef][ISI][Medline]
8. Chen DK, McGeer A, de Azavedo JC, Low DE. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network. N Engl J Med. 1999;341 :233 –239[Abstract/Free Full Text]
9. Ho PL, Que TL, Tsang DN, Ng TK, Chow KH, Seto WH. Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrob Agents Chemother. 1999;43 :1310 –1313[Abstract/Free Full Text]
10. 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[CrossRef][ISI][Medline]
11. Zervos MJ, Hershberger E, Nicolau DP, et al. Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, 1991–2000. Clin Infect Dis. 2003;37 :1643 –1648[CrossRef][ISI][Medline]
12. Mullen CA. Ciprofloxacin in treatment of fever and neutropenia in pediatric cancer patients. Pediatr Infect Dis J. 2003;22 :1138 –1142[ISI][Medline]
13. Cao XT, Kneen R, Nguyen TA, Truong DL, White NJ, Parry CM. A comparative study of ofloxacin and cefixime for treatment of typhoid fever in children. The Dong Nai Pediatric Center Typhoid Study Group. Pediatr Infect Dis J. 1999;18 :245 –248[CrossRef][ISI][Medline]
14. Zimbabwe, Bangladesh, South Africa (Zimbasa) Dysentery Study Group. Multicenter, randomized, double-blind clinical trial of short course versus standard course oral ciprofloxacin for Shigella dysenteriae type 1 dysentery in children. Pediatr Infect Dis J. 2002;21 :1136 –1141[ISI][Medline]
15. Leibovitz E, Janco J, Piglansky L, et al. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children. Pediatr Infect Dis J. 2000;19 :1060 –1067[ISI][Medline]
16. Safdar M, Said A, Gangnon RE, Maki DG. Risk of hematolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA. 2002;288 :996 –1001[Abstract/Free Full Text]
17. Johansson A, Berglund L, Gothefors L, Sjostedt A, Tarnvik A. Ciprofloxacin for treatment of tularemia in children. Pediatr Infect Dis J. 2000;19 :449 –453[CrossRef][ISI][Medline]
18. Saez-Llorens X, McCoig C, Feris JM, et al. Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin. Pediatr Infect Dis J. 2002;21 :14 –22[ISI][Medline]
19. Leibovitz E, Piglansky L, Raiz S, et al. Bacteriologic and clinical efficacy of oral gatifloxacin for the treatment of recurrent/nonresponsive acute otitis media: an open label, noncomparative, double tympanocentesis study. Pediatr Infect Dis J. 2003;22 :943 –949[ISI][Medline]
20. Arguedas A, Sher L, Lopez E, et al. Open label, multicenter study of gatifloxacin treatment of recurrent otitis media and acute otitis media treatment failure. Pediatr Infect Dis J. 2003;22 :949 –956[ISI][Medline]
21. Cipro (ciprofloxacin hydrochloride) [package insert]. West Haven, CT: Bayer Pharmaceutical Corporation; 2004. Available at: www.fda.gov/cder/foi/label/2004/19537s049,19857s031,19847se5-027,20780se5-013_cipro_lbl.pdf. Accessed February 3, 2005
22. Grady R. Safety profile of quinolone antibiotics in the pediatric population. Pediatr Infect Dis J. 2003;22 :1128 –1132[ISI][Medline]
23. Burstein GR, Berman SM, Blumer JL, Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis. 2002;35(suppl 2) :S191 –S199
24. Yee CL, Duffy C, Gerbino PG, Stryker S, Noel GJ. Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin. Pediatr Infect Dis J. 2002;21 :525 –529[CrossRef][ISI][Medline]
25. Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003;36 :1404 –1410[CrossRef][ISI][Medline]
26. US Preventive Services Task Force. Appendix A: task force ratings. In: Guide to Clinical Preventive Services. 2nd ed. Rockville, MD: US Preventive Services Task Force, US Department of Health and Human Services; 1996:862

This article has been cited by other articles:

				K. A. Pesaturo, E. Z. Ramsey, P. N. Johnson, and L. M. Taylor Introduction to pediatric pharmacy practice: Reflections of pediatrics practitioners Am. J. Health Syst. Pharm., July 15, 2008; 65(14): 1314 - 1319. [Full Text] [PDF]

				M. E. Pichichero and J. R. Casey Emergence of a Multiresistant Serotype 19A Pneumococcal Strain Not Included in the 7-Valent Conjugate Vaccine as an Otopathogen in Children JAMA, October 17, 2007; 298(15): 1772 - 1778. [Abstract] [Full Text] [PDF]

				E. Protzko, L. Bowman, M. Abelson, A. Shapiro, and for the AzaSite Clinical Study Group Phase 3 Safety Comparisons for 1.0% Azithromycin in Polymeric Mucoadhesive Eye Drops versus 0.3% Tobramycin Eye Drops for Bacterial Conjunctivitis Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3425 - 3429. [Abstract] [Full Text] [PDF]

				K. Pfister, D. Mazur, J. Vormann, and R. Stahlmann Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats Antimicrob. Agents Chemother., March 1, 2007; 51(3): 1022 - 1027. [Abstract] [Full Text] [PDF]

				J. Bradley Fluoroquinolones in children addressed in AAP policy AAP News, September 1, 2006; 27(9): 1 - 5. [Full Text]

P³Rs:

This Article Abstract Full Text (PDF) P3Rs: Submit a response P3Rs: View responses Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Related Collections Therapeutics & Toxicology

	Home | My Pediatrics | Journal Information | Current Issue | Past Issues | Subscriptions & Services | Contact Us Click here for faster international access © 2006 American Academy of Pediatrics. All rights reserved.