Skip Navigation

Ciprofloxacin for the Treatment of Uncomplicated Gonorrhea Infection in Adolescents: Does the Benefit Outweigh the Risk?

  1. Gale R. Burstein1,
  2. Stuart M. Berman1,
  3. Jeffery L. Blumer2, and
  4. John S. Moran1
  1. 1Centers for Disease Control and Prevention, Atlanta, Georgia
  2. 2Case Western Reserve University, Cleveland, Ohio
  1. Dr. Gale R. Burstein, Division of HIV and AIDS Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd., Mail Stop E-46, Atlanta, GA 30333 (gib5{at}cdc.gov).
 
Next Section

Abstract

The highest rates of reported gonorrhea infections occur among adolescent females aged 15–19 years. Among the Centers for Disease Control and Prevention (CDC)–recommended single-dose gonorrhea treatment regimens, ciprofloxacin, a fluoroquinolone antibiotic, is approximately half the cost of other CDC-recommended oral treatment regimens. Fluoroquinolone use in patients aged <18 years has been limited because of irreversible articular cartilage damage demonstrated in large, weight-bearing joints of young animals. We reviewed the medical literature to assess whether the risks of a single 500-mg dose of ciprofloxacin to treat uncomplicated gonorrhea infection in adolescents appears to outweigh the benefits. We found no reports of irreversible cartilage toxicity or age-associated adverse events in 5236 human children and adolescents (aged 5 days–24 years) treated with a total of 5486 courses of fluoroquinolones.

The highest rates of reported gonorrhea infections occur among adolescent females aged 15–19 years [1]. Sociodemographic studies have mapped endemic gonorrhea and sporadic gonorrhea cases to impoverished urban areas with limited resources [2, 3]. Therefore, an inexpensive, effective, single-dose antibiotic would be beneficial for the treatment and control of gonorrhea.

Although Neisseria gonorrhoeae was once responsive to a wide spectrum of antibiotics, treatment options are now limited. In response to the progressive rise in N. gonorrhoeae resistance to penicillin and tetracycline, the Centers for Disease Control and Prevention (CDC) published guidelines in 1987 that include recommendations to discontinue use of these classes of antibiotics for treatment of gonorrhea infection [4]. Antimicrobial resistance of N. gonorrhoeae remains a critical concern for gonorrhea treatment. Overall, 28.1% of isolates collected in 1999 by the CDC's Gonococcal Surveillance Project were resistant to penicillin, tetracycline, or both [1].

Some providers use azithromycin for the treatment of adolescent gonorrhea infection [5]. Published studies that have evaluated a 1-g single dose of azithromycin for gonorrhea treatment have demonstrated a suboptimal cure rate of only 93% [6–8]. A single 2-g azithromycin dose is effective in the treatment of uncomplicated gonorrhea infection, but the high frequency of gastrointestinal side effects and the high cost prohibit its practical use [6, 9].

The CDC's 1998 Guidelines for Treatment of Sexually Transmitted Diseases recommended the use of either 2 fluoroquinolone antimicrobials or 2 cephalosporins for the treatment of uncomplicated gonorrhea infection [6]. Among these recommended regimens, ciprofloxacin, a fluoroquinolone antibiotic, is one of the most affordable. Although ciprofloxacin has been used extensively in children with pulmonary exacerbations due to cystic fibrosis, recommendations for fluoroquinolone use in patients aged <18 years have been limited [10, 11] because of documented irreversible articular cartilage damage in the large, weight-bearing joints of young animals [12–18].

Quinolone-induced arthropathy has been demonstrated in all immature animal species tested, including dogs, rabbits, rats, and guinea pigs [13, 15]. The effect on cartilage varies by animal species, age, quinolone type, and dose. Dogs are more susceptible to cartilage damage than other animal species, such as the rat [13, 15–18]. Young, skeletally immature animals primarily develop quinolone arthropathy [13, 15, 16, 19]. In juvenile beagle dogs, the period of maximal susceptibility corresponds to the period of maximal growth [16]. Most data have not demonstrated damage to older dogs. Although a study demonstrated microscopic adult cartilage changes after 12 months of continuous treatment with perfloxacin, a more arthropathic quinolone [17], we found no data that have attempted to demonstrate ciprofloxacin-induced cartilage toxicity in an adult animal. Ofloxacin produces damage at lower doses than ciprofloxacin [16, 17]. The minimum canine arthropathic dose of ciprofloxacin has been reported as 30 mg/kg/day, whereas the minimum dose for ofloxacin is reported as 10 mg/kg/day [16, 17]. Higher fluoroquinolone doses produce more extensive articular damage. For example, young beagles treated with ciprofloxacin 200 mg/kg/day were more likely to exhibit articular cartilage lesions than those treated with 100 mg/kg/day [18].

Clinically, the fluoroquinolone-associated cartilage toxicity in animal models has mainly been seen in large, weight-bearing joints. Affected dogs become lame, with sporadic synovial effusion after 1–7 days of quinolone treatment [16]. In addition, affected dogs exhibit an altered standing posture characterized by hyperextension of weight-bearing joints [16]. Histopathologic damage, such as blisters, fissures, and erosions accompanied by joint effusions, and MRI abnormalities are correlated with clinical findings [13, 15, 16, 18, 19].

Adolescents aged <18 years are at great risk for gonorrhea. This population would clearly benefit from greater availability of an inexpensive, effective gonorrhea treatment but are restricted from the use of fluoroquinolones because of a theoretical risk of associated cartilage toxicity observed in animals. In the present article, we review empirical evidence from the medical literature to assess whether (1) the theoretical barrier to the use of fluoroquinolones in patients aged <18 years is justified and (2) changes in fluoroquinolone treatment recommendations for uncomplicated gonorrhea infection should be made in future guidelines for treatment of sexually transmitted diseases (STDs).

Previous SectionNext Section

Materials and Methods

We conducted a search of the literature from 1966 to 2000, using the MEDLINE 2000 database of the US National Library of Medicine. The terms “anti-infective agents,” “fluoroquinolones,” “ciprofloxacin,” and “ofloxacin” (as subjects) and “adverse effects,” “toxicity,” and “contraindications” (as key words) were searched in titles and abstracts. We found 69 references. We limited the search to articles concerning human subjects in English, French, or German. We excluded articles if data were not provided for at least one of the recommended gonorrhea treatment regimens [6], if the age of the subjects was either undefined or if the majority of subjects were aged <1 or ⩾18 years, or if subjects were taking additional antimicrobials during the study period. This reduced the number of citations to 14. We obtained an additional 17 citations from article references that had not been identified by the original search.

We included studies that provided data on the adverse effects of fluoroquinolone use in adolescents through their mid-20s. We summarized articles and recorded information on evaluation methodology, subject age, diagnoses, results, and study conclusions. Length of fluoroquinolone exposure and duration of follow-up were presented in months.

To estimate cost of the drugs included in the CDC-recommended gonorrhea treatment regimens, the Department of Health and Human Services Supply Service Center catalogue [20] was used for “low-end” drug-cost estimates, such as those experienced by public-sector purchasers or managed care organizations; the Henry Schein Medical catalogue [21] was used for estimates of “high-end” drug costs, such as those incurred for purchase from a private-sector pharmacy. We drew conclusions on the basis of evidence from the literature for future changes in recommendations of adolescent fluoroquinolone use for the treatment of gonorrhea infection.

Previous SectionNext Section

Results

Studies with histopathologic or radiological end points. We reviewed 10 studies that, radiographically or pathologically by autopsy, evaluated pediatric and adolescent patients aged 5 days–24 years who were treated with ciprofloxacin or ofloxacin for 7 days–10 months [22–31]. These studies found no evidence of the cartilaginous pathology described in the original fluoroquinolone animal studies (table 1) [12–19]. Schaad et al. [31] performed autopsies of the left knee on 2 children aged 7 and 13 years with cystic fibrosis treated with 9–10 months of ciprofloxacin. He found no histopathologic cartilage lesions.

Table 1
Table 1

Radiographic, anatomic, and histopathologic assessment of joints among adolescents and children treated with fluoroquinolones.

Of the 9 radiographic studies that evaluated large joints, 5 used X-ray and 5 used MRI [22–30]. None reported pathologic changes detected as a direct effect of therapy. One prospective study followed 29 pediatric patients with cystic fibrosis who had received 7–10 days of antibiotic treatment; 14 were treated with ciprofloxacin or ofloxacin, and 15 were treated with other standard cystic fibrosis antibiotic regimens [30]. The authors found similar proportions of abnormal knee X-ray and MRI findings in both treatment groups after completion of therapy (cases, 43% abnormal X-rays and 50% abnormal MRI; controls, 33% abnormal X-rays and 70% abnormal MRI.) Because children with cystic fibrosis are predisposed to joint abnormalities, this study failed to demonstrate that fluoroquinolone was associated with any additional risk of joint damage [32, 33].

The fluoroquinolone-induced irreversible articular cartilage damage observed in large weight-bearing joints of juvenile animals evolves rapidly, within days [12, 15, 16]. However, irreversible fluoroquinolone-induced cartilage toxicity was not demonstrated during treatment and follow-up time (range, 0.3–10 months) among the 201 youth reported in the aforementioned studies (table 1). Such a finding should indicate the problems with extrapolating from animal data to humans and provide evidence, at the very least, that if fluoroquinolones do have adverse effects on the cartilage of children and adolescents, those effects are minimal compared with those found among animals.

Clinical research studies with adverse events as end points. A variety of adverse events associated with fluoroquinolone use have been described among pediatric and adolescent patients (table 2) [22, 25–29, 34–49]. The most common complaints were gastrointestinal (e.g., diarrhea and vomiting), musculoskeletal (e.g., arthralgias), dermatologic (e.g., photosensitivity rash), and hepatic enzyme elevation. Many of these studies were conducted among patients whose underlying diseases, such as cystic fibrosis or typhoid fever, may have caused the reported adverse events. All of the adverse events were self-limited. Six of 22 studies failed to detect any fluoroquinolone-associated adverse events among 118 pediatric and adolescent subjects [25, 37, 39, 42, 47, 49].

Table 2
Table 2

Studies reporting adverse events associated with fluoroquinolone use among adolescents and children.

The spectrum and frequency of adverse events associated with fluoroquinolone use among pediatric and adolescent patients are compared with reports of adverse events among individuals aged ⩾18 years as listed in the Physicians Desk Reference (PDR) in table 3. The most frequently reported fluoroquinolone-associated events listed in PDR include gastrointestinal complaints (nausea, diarrhea, vomiting, and abdominal pain/discomfort), CNS symptoms (headache and restlessness), dermatologic changes (rash), and elevated hepatic enzymes [10]. Although the spectrum of adverse events reported in adults is similar to those found among patients aged <18 years, the frequency of these events is greater among pediatric age groups. This may be due to reporting bias, because most pediatric patients in these studies had diagnoses that would render them more susceptible to gastrointestinal, dermatologic, and CNS symptoms and musculoskeletal complaints, such as typhoid fever and cystic fibrosis. Musculoskeletal complaints occurred more frequently among pediatric and adolescent patients than among adults. It is important to note that permanent arthropathy, the theoretical adverse event that restricts fluoroquinolone use among patients aged <18 years, was not reported in any of the scientific studies or the PDR.

Table 3
Table 3

Adverse events associated with fluoroquinolone use among adolescents and children as reported in the literature and by the Physicians Desk Reference (PDR) [10].

Case reports of adverse events. Various reported pediatric and adolescent fluoroquinolone-associated adverse events, such as anaphylactic reaction, dystonic reaction, sleep disturbance, arthralgias, and hallucinations, have also been reported to occur in fluoroquinolone-treated adults (table 4) [10, 23, 24, 50–53]. Benign intracranial hypertension, reported by Winrow et al. [54] in a 14-year-old girl treated with ciprofloxacin for a pulmonary exacerbation of cystic fibrosis, was not listed in the PDR [10]. However, intracranial hypertension has been reported in infants and children using naldixic acid, a quinolone antibiotic [55].

Table 4
Table 4

Case reports of adverse events associated with quinolone use among adolescents and children.

Published recommendations. The American Academy of Pediatrics recommends fluoroquinolone regimens for the treatment of gonorrhea genital infections only for patients aged ⩾18 years who weigh >100 lbs (45 kg) [11, 56]. Other professional medical organizations, such as the American College of Obstetricians and Gynecologists and the American Academy of Family Physicians, have not published gonorrhea treatment recommendations.

Costs of gonorrhea treatment regimens. The costs for a course of ciprofloxacin range between $1.05 and $4.66 per curative dose (table 5) [20, 21]. Treatment costs are substantially greater with other recommended therapies, such as ofloxacin ($2.39–$6.01) and cefixime ($4.78–$6.44). Listed ceftriaxone prices ($2.60–$10.25) do not include the costs incurred with dispensing an intramuscular medication.

Table 5
Table 5

Costs per curative dose for Centers for Disease Control—recommended treatment of N. gonorrhoeae.

Previous SectionNext Section

Discussion

Adolescents have the highest reported rates of gonorrhea; the reported 1999 rates were 738.1 out of 100,000 among females aged 15–19 years [1]. Ciprofloxacin, a fluoroquinolone antibiotic, is an effective single-dose treatment for uncomplicated gonorrhea genital infections [57]. However, the theoretical risks of clinically and histopathologically apparent irreversible juvenile animal cartilage damage, evident within a few days of treatment, have restricted the use of this drug among adolescents aged <18 years [12, 14–16, 18, 19]. Because gonorrhea rates are high in this population and STD control resources are limited, it is appropriate to consider whether the theoretical risks outweigh the therapeutic and economic benefits of ciprofloxacin use for treatment of gonorrhea infections in adolescents.

The 10 identified studies that have evaluated children and adolescents exposed to multiple-day doses of fluoroquinolones through objective radiological or histological methods demonstrated no evidence of irreversible cartilage damage [22–31]. Other studies that have assessed for fluoroquinolone-induced cartilage damage by more passive means did not report any evidence of clinically apparent irreversible damage among 4999 children and adolescents [34–49].

Age and quantity of drug exposure influenced the risk of animal joint damage. In beagle dogs, the period of maximal susceptibility corresponds to the period of maximal growth [16]. The vast majority of sexually active adolescents treated for gonorrhea will have passed their period of maximal growth. The recommended ciprofloxacin gonorrhea treatment regimen is a single 500-mg dose [6]. This dose calculates to 10 mg/kg in an individual who weighs 50 kg. The minimum ciprofloxacin dose associated with juvenile dog cartilage damage is 30 mg/kg/day over multiple days. The risk of a single ⩽10-mg/kg ciprofloxacin dose causing an adverse event in a skeletally mature adolescent should be much lower than the risk associated with multiple dose regimens dispensed to skeletally immature animals.

Our MEDLINE 2000 database literature search on this topic proved to be an insensitive method for identifying relevant journal articles. Although we may have missed other published studies that described pediatric fluoroquinolone-associated adverse events, it is unlikely that both our original search results and supplemental sources missed a study with significantly different findings.

Conclusions based on a literature review of fluoroquinolone-associated adverse events are also limited by the reality that a clinical trial is unlikely to have adequate power to detect a rare and serious adverse event. However, neither studies that followed 201 fluoroquinolone-exposed youth from 0.3 to 10 months nor case reports have described serious or irreversible cartilage damage associated with pediatric fluoroquinolone use. In light of the fact that the concerns of fluoroquinolone use and joint damage are well known, one might expect that if such a case had come to medical attention, its existence would have been reported [14, 15].

Limitations of the studies reviewed include sensitivity of methods used to detect cartilage damage. Three of the studies used X-ray to objectively measure joint-related adverse events [22–24]. X-ray may not be the most sensitive test to detect cartilage damage. However, more sensitive objective methods, MRI and autopsy, also failed to demonstrate evidence of irreversible fluoroquinolone-related cartilage damage [25–31].

These data are also limited by the specificity of the criteria used to assess for fluoroquinolone-related adverse events. Most of these studies involved subjects with an underlying disease known to cause joint pain, such as cystic fibrosis, typhoid fever, sepsis, and cancer. Therefore, it may have been difficult to differentiate drug-related events from disease-related events. However, Church et al. [34] were able to demonstrate that patients with cystic fibrosis experienced the same rate of joint-related events regardless of fluoroquinolone exposure. In this randomized controlled trial of patients aged <18 years treated for pulmonary exacerbations of cystic fibrosis, subjects who received ciprofloxacin did not differ in treatment-associated musculoskeletal adverse events from the control group, which received standard therapy (21% vs. 22%).

The cost data we used may not be generalizable to all clinical settings. However, these quotes are representative estimates derived from major pharmaceutical suppliers that service the public [20] and private sectors [21]. Ciprofloxacin, a fluoroquinolone antibiotic, is the least expensive among the recommended oral regimens. Although the lower-end costs of ceftriaxone overlap with higher-end costs of ciprofloxacin, an intramuscular regimen incurs other dispensing costs, such as cost of syringes, needles, and nursing time. In addition, painful treatment may deter the adolescent from seeking future STD treatment services. Even though the absolute price per dose between recommended ciprofloxacin and the cefixime regimen differs by only a few dollars, the proportional difference is half. Because gonorrhea prevalence is relatively higher among adolescents, clinics that provide STD treatment services would expect to dispense a significant proportion of gonorrhea treatment to patients aged <18 years. Therefore, total programmatic costs for gonorrhea control would be reduced if fluoroquinolone use were not limited by age.

In light of the failure to demonstrate associated cartilage toxicity in fluoroquinolone-exposed children, the Food and Drug Administration is reassessing its restrictions on pediatric ciprofloxacin use. Ciprofloxacin has recently been approved for postexposure prophylaxis for pediatric inhalational anthrax, and the drug is currently being studied in phase 3 and 4 clinical trials for treatment of pediatric otitis media (C. Skowronski, personal communication).

In conclusion, the benefits of a single 500-mg dose of ciprofloxacin for the treatment of uncomplicated adolescent gonorrhea infection appear to outweigh the theoretical risks. Gonorrhea is a significant health problem among adolescents. Ciprofloxacin is an effective and inexpensive treatment option for uncomplicated genital gonorrhea infections. The cost of a single dose of ciprofloxacin is approximately half the cost of the other oral nonfluoroquinolone, CDC-recommended single-dose gonorrhea treatment regimens. Irreversible cartilage toxicity, the theoretical risk that limits its use among the age group with the highest reported gonorrhea prevalence, has not been demonstrated in 5236 growing children or skeletally mature adolescents (aged 5 days–24 years) treated with 5486 courses of fluoroquinolones. Providers should consider these risks and benefits when managing uncomplicated gonorrhea infections in adolescents.

Previous SectionNext Section

Acknowledgments

We gratefully acknowledge Patrick Deere for help with the manuscript, Carolyn Skowronski for supply of references, and Leonard Weiner for review of the manuscript.

Previous Section
 

References

  1. ↵
    1. Division of STD Prevention
    . Sexually transmitted disease surveillance, 1999. Atlanta: Centers for Disease Control and Prevention; 2000.
  2. ↵
    1. Cohen D,
    2. Spear S,
    3. Scribner R,
    4. Kissinger P,
    5. Mason K,
    6. Wildgen J
    . "Broken windows" and the risk of gonorrhea. Am J Public Health 2000;90:181-3.
    FREE Full Text
  3. ↵
    1. Eng TR,
    2. Butler WT
    1. Institute of Medicine
    . Factors that contribute to the hidden epidemic. In: Eng TR, Butler WT, editors. The hidden epidemic. Washington, DC: National Academy Press; 1997. p. 69-117.
  4. ↵
    1. Centers for Disease Control
    . Antibiotic-resistant strains of Neisseria gonorrhoeae. MMWR Morb Mortal Wkly Rep 1987;36((Suppl 5)):1S-18S.
  5. ↵
    1. McGregor J,
    2. Stamm C
    . Diagnosing and treating STDs in young women. Contemp Pediatr 2001;18(Supplement_2):53-67.
  6. ↵
    1. Centers for Disease Control and Prevention
    . Guidelines for treatment of sexually 1998 transmitted diseases. MMWR Morb Mortal Wkly Rep 1998;47:59-70.
    Medline
    1. Steingrimsson O,
    2. Olafsson JH,
    3. Thorarinsson H,
    4. Ryan RW,
    5. Johnson RB,
    6. Tilton RC
    . Azithromycin in the treatment of sexually transmitted diseases. J Antimicrob Chemother 1990;25(Suppl A):109-14.
    Abstract/FREE Full Text
  8. ↵
    1. Waugh M
    . Open study of the safety and efficacy of a single oral dose of azithromycin for the treatment of uncomplicated gonorrhoea in men and women. J J Antimicrob Chemother 1993;31(Suppl E):193-8.
    CrossRef
  9. ↵
    1. Handsfield HH,
    2. Dalu ZA,
    3. Douglas JD,
    4. McCarty JM,
    5. Schlossberg D
    . Multicenter trial of single-dose azithromycin vs ceftriaxone in the treatment of uncomplicated gonorrhea. Sex Transm Dis 1994;21:107-11.
    MedlineWeb of Science
  10. ↵
    Physicians desk reference. 55th ed. Montvale, NJ: Medical Economics Company Inc.; 2000. CIPRO® (ciprofloxacin hydrochloride) tablets; p. 847-52.
  11. ↵
    1. Pickering LK
    1. American Academy of Pediatrics
    . Fluoroquinolones. In: Pickering LK, editor. 2000 red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000. p. 645.
  12. ↵
    1. Schaad UB,
    2. Salam MA
    . 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.
    MedlineWeb of Science
  13. ↵
    1. Burkhardt JE,
    2. Walterspiel JN,
    3. Schaad UB
    . Quinolone arthropathy in animals versus children. Clin Infect Dis 1997;25:1196-204.
    Abstract/FREE Full Text
  14. ↵
    1. Echols RM
    . Introduction: historical perspective—use of ciprofloxacin in children. Pediatr Infect Dis J 1997;16:89-90.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Warren RW
    . Rhematologic aspects of pediatric cystic fibrosis patients treated with fluoroquinolones. Pediatr Infect Dis J 1997;16:118-22.
    CrossRefMedlineWeb of Science
  16. ↵
    1. Burkhardt JE
    . Review of quinolone arthropathy in the dog. Chemotherapie J 1996;5(Suppl 13):14-8.
  17. ↵
    1. Christ W,
    2. Lehnert T,
    3. Ulbrich B
    . Specific toxicologic aspects of the quinolones. Rev Infect Dis 1988;10(Suppl):S141-6.
    Medline
  18. ↵
    1. Schluter G
    . Proceedings from the 1st International Ciprofloxacin Workshop (Leverkusen, Germany). Amsterdam: Excerpto Medica; 1986. Toxicology of ciprofloxacin [abstract xx]; p. 61-7.
  19. ↵
    1. Stahlmann R,
    2. Forster C,
    3. Van Sickle D
    . Quinolones in children. Are concerns over arthropathy justified?. Drug Saf 1993;9:397-403.
  20. ↵
    HHS SSC medical supply catalog 2000. Perry Point, MD: US Department of Health and Human Services Supply Service Center; 2000.
  21. ↵
    1. Henry Schein medical catalogue
    . The source 2000 update. Melville, NY: Henry Schein, Inc.; 2000.
  22. ↵
    1. Rubio TT
    . Ciprofloxacin in the treatment of Pseudomonas infection in children with cystic fibrosis. Diagn Microbiol Infect Dis 1990;13:153-5.
    CrossRefMedlineWeb of Science
  23. ↵
    1. Jawad ASM
    . Cystic fibrosis and drug-induced arthropathy [letter]. Brit J Rheumatol 1989;28:179-80.
    FREE Full Text
  24. ↵
    1. Alfaham M,
    2. Holt ME,
    3. Goodchild MC
    . Arthropathy in a patient with cystic fibrosis taking ciprofloxacin [letter]. Br Med J 1987;295:699.
    FREE Full Text
  25. ↵
    1. Redmond A,
    2. Sweeney L,
    3. MacFarland M,
    4. Mitchell M,
    5. Daggett S,
    6. Kubin R
    . Oral ciprofloxacin in the treatment of Pseudomonas exacerbations of paediatric cystic fibrosis: clinical efficacy and safety evaluation using magnetic resonance image scanning. J Int Med Res 1998;26:304-12.
    MedlineWeb of Science
    1. Pradham KM,
    2. Arora NK,
    3. Susheela AK,
    4. Bhan MK
    . Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatr 1995;84:555-60.
    MedlineWeb of Science
    1. Richard DA,
    2. Nousia-Arvanitakis S,
    3. Sollich V,
    4. Hampel BJ,
    5. Sommerauer B,
    6. Schaad UB
    . Oral ciprofloxacin vs. intravenous cetazidime plus tobramycin in pediatric cystic fibrosis patients: comparison of antiseudomonas efficacy and assessment of safety with ultrasonography and magnetic resonance imaging. Pediatr Infect Dis J 1997;16:572-8.
    CrossRefMedlineWeb of Science
    1. Singh UK,
    2. Sinha RK,
    3. Prasad B,
    4. Chakrabarti B,
    5. Sharma SK
    . Ciprofloxacin in children: is arthropathy a limitation? Indian J Pediatr 2000;67:386-7.
    CrossRefMedline
  29. ↵
    1. Schaad UB,
    2. Stoupis C,
    3. Wedgwood J,
    4. Tschaeppeler H,
    5. Vock P
    . Clinical, radiologic and magnetic resonance monitoring for skeletal toxicity in pediatric patients with cystic fibrosis receiving a three-month course of ciprofloxacin. Pediatr Infect Dis J 1991;10:723-9.
    MedlineWeb of Science
  30. ↵
    1. Danisovicova A,
    2. Brezina M,
    3. Belan S,
    4. et al
    . Magnetic resonance imaging in children receiving quinolones: no evidence of quinolone-indced arthropathy. Chemotherapy 1994;40:209-14.
    MedlineWeb of Science
  31. ↵
    1. Schaad UB,
    2. Sander E,
    3. Wedgwood J,
    4. Schaffner T
    . Morphologic studies for skeletal toxicity after prolonged ciprofloxacin therapy in two juvenile cystic fibrosis patients. Pediatr Infect Dis J 1992;11:1047-49.
    MedlineWeb of Science
  32. ↵
    1. Phillips BM,
    2. David TJ,
    3. et al
    . Pathogenesis and management of arthropathy in cystic fibrosis. J R Soc Med 1986;79(Suppl 12):44-50.
    MedlineWeb of Science
  33. ↵
    1. Dixey J,
    2. Redington AN,
    3. Butler RC,
    4. et al
    . The arthropathy of cystic fibrosis. Ann Rheum Dis 1988;47:218-33.
    Abstract/FREE Full Text
  34. ↵
    1. Church DA,
    2. Kanga JF,
    3. Kuhn RJ,
    4. et al
    . Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. Pediatr Infect Dis J 1997;16:97-105.
    CrossRefMedlineWeb of Science
    1. Rubio TT,
    2. Miles MV,
    3. Lettieri JT,
    4. Kuhn RJ,
    5. Echols RM,
    6. Church DA
    . Pharmacokinetic disposition of sequential intravenous/oral ciprofloxacin in pediatric cystic fibrosis patients with acute pulmonary exacerbation. Pediatr Infect Dis J 1997;16:112-7.
    CrossRefMedlineWeb of Science
    1. Schaad UB,
    2. Wedgwood J,
    3. Ruedeberg A,
    4. Kraemer R,
    5. Hampel B
    . Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis. Pediatr Infect Dis J 1997;16:106-11.
    CrossRefMedlineWeb of Science
  37. ↵
    1. Sen S,
    2. Goyal Rs,
    3. Dev R
    . Ciprofloxacin in the management of multiple drug resistant typhoid fever. Indian Pediatr 1991;28:417-9.
    Medline
    1. Salam MA,
    2. Dhar U,
    3. Khan WA,
    4. Bennish ML
    . Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Lancet 1998;352:522-7.
    CrossRefMedlineWeb of Science
  39. ↵
    1. Naccari F,
    2. Salpietro DC,
    3. De Sarro A,
    4. Masaracchio A,
    5. Barberi I
    . Tolerance and pharmacokinetics of ciprofloxacin in the chick. Preliminary experience in subjects of pediatric age with urinary tract infections. Res Commun Molec Pathol Pharmacol 1998;99:187-92.
    MedlineWeb of Science
    1. Lang R,
    2. Goshen S,
    3. Raas-Rothschild A,
    4. et al
    . Oral ciprofloxacin in the management of chronic suppurative otitis media without cholesteatoma in children: preliminary experience in 21 children. Pediatr Infect Dis J 1992;11:925-9.
    MedlineWeb of Science
    1. Vinh H,
    2. Wain J,
    3. Hanh VTN,
    4. et al
    . Two or three days of ofloxacin treatment for uncomplicated multidrug-resistant typhoid fever in children. Antimicrob Agents Chemother 1996;40:958-61.
    Abstract/FREE Full Text
  42. ↵
    1. Black A,
    2. Redmond AOB,
    3. Steen HJ,
    4. Oborska IT
    . Tolerance and safety of ciprofloxacin in paediatric patients. J Antimicrob Chemother 1990;26(Suppl F):25-9.
    Abstract/FREE Full Text
    1. Jick S
    . Ciprofloxacin safety in a pediatric population. Pediatr Infect Dis J 1997;16:130-4.
    CrossRefMedlineWeb of Science
    1. Hampel B,
    2. Hullmann R,
    3. Schmidt H
    . Ciprofloxacin in pediatrics: worldwide clinical experience based on compassionate use—safety report. Pediatr Infect Dis J 1997;16:127-9.
    CrossRefMedlineWeb of Science
    1. Chysky V,
    2. Kapila K,
    3. Hullmann R,
    4. Arcieri G,
    5. Schacht P,
    6. Echols R
    . Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use. Empahsis on joint evaluation. Infection 1991;19:289-96.
    CrossRefMedlineWeb of Science
    1. Thomsen LL,
    2. Paerregaard A
    . Treatment with ciprofloxacin in children with typhoid fever. Scand J Infect Dis 1998;30:355-7.
    CrossRefMedlineWeb of Science
  47. ↵
    1. Pertuiset E,
    2. Lenoir G,
    3. Jehanne M,
    4. Douchain F,
    5. Guillot M,
    6. Menkes CJ
    . Joint tolerance of pefloxacin and ofloxacin in children and adolescents with cystic fibrosis [in French]. Rev Rhumatol 1989;56:735-40.
    1. El-Sherbini A
    . An outbreak of typhoid fever resistant to chloramphenicol and other drugs in Gharbeya Governorate in Egypt. J Trop Pediatr 1991;38:331-4.
  49. ↵
    1. Arico M,
    2. Bossi G,
    3. Casselli D,
    4. et al
    . Long term magnetic resonance survey of cartilage damage in leukemic children treated with fuoroquinolones [letter]. Pediatr Infect Dis J 1995;14:713-4.
    CrossRefMedlineWeb of Science
  50. ↵
    1. Miller MS,
    2. Gaido F,
    3. Rourk MH Jr,
    4. Spock A
    . Anaphylactoid reactions to ciprofloxacin in cystic fibrosis patients [letter]. Pediatr Infect Dis J 1991;10:164-5.
    CrossRefMedlineWeb of Science
    1. Singh J,
    2. Agarwa AK,
    3. Sudrania SP
    . Extrapyramidal syndrome following ciprofloxacin treatment [letter]. Indian Pediatr 1994;31:608-9.
    Medline
    1. Upton C
    . Sleep disturbances in children treated with ofloxacin [letter]. Br Med J 1994;309:1411.
    FREE Full Text
  53. ↵
    1. Rabatoli PV,
    2. D'Souza RSD,
    3. Chume VG
    . An unusual hallucination with norfloxacin [letter]. J Assoc Phys India 1996;44:504.
  54. ↵
    1. Winrow AP,
    2. Supramaniam G
    . Benign intracranial hypertension after ciprofloxacin administration. Arch Dis Child 1990;65:1165-6.
    Abstract/FREE Full Text
  55. ↵
    Physicians desk reference. 55th ed. Montvale, NJ: Medical Economics Company Inc.; 2000. NegGram® (naldixic acid); p. 2857-8.
  56. ↵
    1. Pickering LK
    1. American Academy of Pediatrics
    . Gonococcal infections. In: Pickering LK, editor. 2000 red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000. p. 254-60.
  57. ↵
    1. Moran JS,
    2. Levine WC
    . Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 1995;20(Suppl 1):S47-65.
    Medline
| Table of Contents

This Article

  1. Clin Infect Dis. (2002) 35 (Supplement 2): S191-S199. doi: 10.1086/342107
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most