INDICES> Ciprofloxacin use in children (3)

["Amanda Van Wyk" <amayeza@pharmail.co.za>]

INDICES> Ciprofloxacin use in children (3)
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Dear Dr Ojoo

Attached please find information from Micromedex on  the use of
ciprofloxacin in children.

Amanda Van Wyk
Amayeza Drug Info Centre
South Africa
Email: amayeza@pharmail.co.za

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QUINOLONE USE IN PEDIATRICS

·        QUINOLONES are not considered a new class of drugs. However, there
are several new agents within this class which show promise in many
resistant strains of bacteria. Documented uses in children include acute
meningitis (Segev et al, 1990), cystic fibrosis infections by pseudomonas
(Black et al, 1990), and multiresistant typhoid (Cheesbrough et al, 1991).
Quinolones are currently contraindicated in children less than 18 years of
age because animal studies have shown lesions and destruction of cartilage
in weight-bearing joints in immature dogs.
·        Adam (1989) reported a retrospective study with 100 patients who
were treated with NALIDIXIC ACID. These children had comparable
roentgenographic studies on the hips and knee joints before and/or during
therapy, then 2 years later. The subjects were compared to a control group
of an equal number of patients with the same diagnosis, but were treated
with different antibiotics. Suitable roentgenographic studies were
available for 50 patients in the control group and 50 patients on nalidixic
acid. No case of drug-induced cartilage damage was found. Neither group
showed any sign of drug-related alteration in the joint building areas
after 13 years of observation. This led to the conclusion that arthropathy
due to quinolones did not occur in children. The disparity between animal
data and humans is most likely due to interspecies differences.
·        In a study by Bannon et al (1989), a multiresistant strain of
Enterobacter cloacae was eradicated in six premature infants using
CIPROFLOXACIN 10 milligrams/kilogram/day. Ciprofloxacin was given
intravenously in 2 divided doses for 14 days to 4 infants, and 21 days to 1
infant. The sixth infant died 9 days after therapy started. All patients
received at least 2 courses of different antibiotic therapy before
ciprofloxacin. All 6 infants were premature and of low birth weight and
were ventilated for lung disease. E cloacae was eradicated in all 6 cases,
although 3 infants died of other causes. There were no side effects
observed in these patients. Ciprofloxacin was recommended at an earlier
stage of the infection when first-line agents are ineffective.
·        Ciprofloxacin was used to treat 2 female children, aged 7 and 13
years, who had cystic fibrosis. Over the course of 3 years, ciprofloxacin
was administered several times, in a dose of 30 milligrams/kilogram/day in
2 divided oral doses. Subsequently these patients died. Autopsy examination
of the left knee revealed no cartilage changes or toxicity (Schaad et al,
1992).
·        Black et al (1990) reported a study by the Cystic Fibrosis Clinic
at the Royal Belfast Hospital; 31 patients were treated with ciprofloxacin
for serious pseudomonas infection. These children had failed to respond to
other antibiotics. Knee measurements were taken before and after each
course of therapy and the patients were monitored for any joint pain or
swelling. There were few adverse reactions in this group. One patient
developed diarrhea, 3 had photosensitivity reactions after long exposures
in the sun, and 1 had a pruritic RASH. Thirteen additional patients were
treated with ciprofloxacin and only one patient developed ARTHRALGIA in the
wrists and ankles that resolved when the drug was discontinued. Although
the findings were encouraging, the author felt caution still needed to be
exercised. Further animal studies indicated blistering of the knee
cartilage in one of 4 juvenile dogs treated with ciprofloxacin 100
milligrams/kilogram/day for 14 days (Schluter, 1989). In light of the lack
of resolution of this question, ciprofloxacin use in children must be
carefully weighed.
·        Martell M et al (1996) demonstrated that ciprofloxacin and
pefloxacin for the "life-saving" treatment of sepsis in preterm infants
were NOT associated with osteo-articular problems or joint deformities.
Three treatment groups were evaluated to assess the affect of quinolones on
growth and development in preterm infants. Group I were treated with
ciprofloxacin (n=2) or pefloxacin (n=5) 12 milligrams/kilogram/day. Group
II (n=7) were also neonates with sepsis, but were treated with other
antibiotics. Group III (n=7) were neonates without an infectious pathology.
Antibiotic therapy was for 10 days and clinical efficacy and toxicity were
measured up to 30 or 42 weeks. None of the groups had any evidence of
osteopathic changes (ie, osteo- articular deformities or joint problems).
In addition, no differences in development (ie, motor, social, or language)
were noted between groups. Group I (quinolones) did show SMALLER weight and
head circumference (p greater than 0.05); although this may have been due
to their severity of illness. This study suggests that quinolones may be
considered as an therapeutic option in the short-term treatment of
"life-saving" infections.
·        According to another review of quinolone use in children involving
over 7,000 patients, quinolones are considered safe in this population.
None of the quinolones reviewed (ciprofloxacin, ofloxacin, and nalidixic
acid) had negative effects on the linear growth of children (Burkhardt et
al, 1997). Another study determined that ciprofloxacin for "life-saving"
treatment in infants was safe; no osteoarticular problems or joint
deformities were observed at 42 months following administration (Gurpinar
et al, 1997).
·        Miller et al (1990) reported adverse reactions in 73 patients
treated with ciprofloxacin at the Duke Cystic Fibrosis Center. Most
patients were treated for 21 days. There were 2 cases of anaphylactoid
reactions. The first was a 16-year-old male who developed generalized
itching, difficulty breathing, and an urticarial rash 1 hour
post-ingestion. The second was a 15-year-old female who 30 minutes
post-ingestion developed an urticarial rash, fever, headache, and vomiting.
Other adverse effects included 2 patients with joint pain.
·        Chevais et al (1987) felt that the contraindications in children
should be reconsidered based on the factors which initiated it and the
benefits that quinolones could offer to pediatrics. The study compared the
benefits versus risks using the new generation of quinolones, including
pefloxacin, ciprofloxacin, ofloxacin, norfloxacin, and enoxacin. The
benefits included marked activity against enterobacteria and gram-negative
organisms, particularly pseudomonas, gram-positive cocci, and certain
anaerobic bacteria. Risks fell into 3 categories: metabolic acidosis in
nursing infants due to immature hepatic enzyme systems, neurologic
accidents which may lead to intracranial hypertension syndrome, and
arthralgia. Although the authors conceded that long-term effects on
articular function and growth are generally unknown, they felt that the
contraindication should be reconsidered whenever the infectious situation
is serious and a sensitive organism is isolated.
·        Stahlman (1990) reviewed the safety profile of quinolones. The
major adverse effects were gastrointestinal (1.8% to 5%), central nervous
system (0.9% to 1.6%), and skin reactions (0.6% to 1.4%). Quinolones can be
mutagenic based on the ability to inhibit DNA gyrase in bacterial cells,
which may be similar to topoisomerases in mammalian cells. No experiments
have demonstrated this in humans. One of the most important toxic effects
is CHONDROTOXICITY. Quinolones have arthropathogenic potential in juvenile
animals and are therefore contraindicated in children, although few
documented cases exist.
·        CONCLUSION:
·        Quinolones offer an advantage over existing antibiotics by
effectively eradicating many multiresistant pathogens. Animal data is not
in concordance with human data with respect to quinolone-induced
arthropathy in infants and children. The data suggest that quinolones may
be indicated if first-line antibiotics have failed and the child and/or
infant is in a life-threatening situation.
·        REFERENCES:
·        1. Adam D: Use of quinolones in pediatric patients. Rev Infect Dis
1989; 11:1113S-1116S.
·        2. Bannon MJ, Stutchfield PR, Weindling AM et al: Ciprofloxacin in
neonatal Enterobacter cloacae septicaemia. Arch Dis Child 1989;
64:1388-1391.
·        3. Black A, Redmond AOB, Steen HJ et al: Tolerance and safety of
ciprofloxacin in pediatric patients. J Antimicrob Chemother 1990; 26(Suppl
F):25-29.
·        4. Burkhardt JE, Walterspiel JN, and Schaad UB: Quinolone
arthropathy in animals versus children. Clin Infect Dis 1997; 25:1196-1204.
·        5. Cheesbrough JS, Ilunga-Mwema F, Green SDR et al: Quinolones in
children with invasive salmonellosis. Lancet 1991; 338:127.
·        6. Chevais M, Reinert P, Rondeau MC et al: Critical risk/benefit
analysis of pefloxacine use in children under 15 years - the problem of
arthralgias. Int J Clin Pharmacol Ther Toxicol 1987; 25:306-309.
·        7. Gurpinar AN, Balkan E, Kilic N et al: The effects of a
fluoroquinolone on the growth and development of infants. J Int Med Res
1997; 25:302-306.
·        8. Martell M, de Ben S, Weinberger M et al: Growth and development
in preterm infants receiving fluoroquinolones. J Perinat Med 1996;
24:287-291.
·        9. Miller MS, Gaido F, Rourke MH et al: Anaphylactoid reactions to
ciprofloxacin in cystic fibrosis patients (letter). Pediatr Infect Dis J
1990; 10:164-165.
·        10. Schaad UB, Sander E, Wedgwood J et al: Morphologic studies for
skeletal toxicity after prolonged ciprofloxacin therapy in two juvenile
cystic fibrosis patients. Pediatr Infect Dis J, 1992; 11:1047-1049.
·        11. Schluter G: Ciprofloxacin: toxicologic evaluation of
additional safety data. Am J Med 1989; 87(Suppl 5A):37S-39S.
·        12. Segev S, Rosen N, Joseph G et al: Pefloxacin efficacy in
gram-negative bacillary meningitis. J Antimicrob Chemother 1990; 26(Suppl
B):187-192.
13. Stahlman R: Safety profile of the quinolones. J Antimicrob Chemother
1990; 26(Suppl D):31-44.

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