Ciprofloxacin in pediatrics: worldwide clinical experience based on compassionate use--safety report.

BACKGROUND: Quinolone-induced cartilage toxicity has been observed in experimental juvenile animal studies and is species- and dose-specific. Accordingly these findings have led to the contraindication of fluoroquinolones in children. Previous data in 634 adolescents and children treated with compassionate use ciprofloxacin demonstrated low rates of reversible arthralgia and a safety profile similar to that for adult patients. OBJECTIVE: This report describes the safety findings in 1795 children who received 2030 treatment courses of intravenous or oral ciprofloxacin. RESULTS: The average doses of intravenous and oral ciprofloxacin in the study population were 8 and 25 mg/kg/day, respectively. Treatment-associated events were reported in 10.9% of children receiving oral ciprofloxacin compared with 18.9% among intravenous recipients. Overall arthralgia occurred during 31 ciprofloxacin treatment courses (1.5%) and the majority of events were of mild to moderate severity and resolved without intervention. More than 60% of arthralgia episodes were in children with cystic fibrosis. CONCLUSION: The adverse event pattern in children receiving ciprofloxacin in this analysis was similar to that observed in adults. Rates of reversible arthralgia were low and unchanged from previously published surveillance data in children.

Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use. Emphasis on joint evaluation.

Six hundred and thirty four adolescents and children aged three days to 17 years treated with ciprofloxacin on a compassionate basis were analysed for drug safety. 62% of the ciprofloxacin courses were given to patients with respiratory tract infection, primarily those with acute pulmonary exacerbation of cystic fibrosis. The mean daily oral dose was 25.2 mg/kg body weight. The duration of treatment ranged from one to 880 days (mean 22.8 days). Because of the arthropathogenic potential of quinolones in juvenile animals special emphasis was placed on the evaluation of musculoskeletal adverse events. Arthralgia considered by the treating physicians to be related to ciprofloxacin was reported in eight children, all of whom were females. Arthralgia resolved in all children. Some of these children were given subsequent courses of ciprofloxacin with no complaints of arthralgia. Overall, the safety profile of ciprofloxacin in children is not substantially different from that of adults.

Safety of oral ciprofloxacin. An update based on clinical trial results.

The safety of ciprofloxacin was established on a data base (compiled through the end of 1988) of 9,473 well-documented treatment courses world-wide. The daily dosages ranged between 200 and 2,000 mg orally. Thirty-eight percent of the patients received doses between 1 and 10 mg/kg body weight, 46 percent between 11 and 20 mg/kg, and the remaining 16 percent more than 20 mg/kg body weight daily. Ciprofloxacin was administered to 4,214 women (45 percent) and 5,252 men (55 percent). The duration of treatment ranged from less than two days to more than 90 days. A 600-mg daily dose of ciprofloxacin was used mostly in Japan (2,341 patients). The daily dose of 1,000 mg was administered chiefly in the United States and Europe (2,288 patients). The age of the patients ranged from less than one year to 99 years (mean, 50.6 years). More than 38 percent were older than 60 years. According to COSTART terminology, the following drug-related side effects were observed in the different organ systems: digestive, 4.9 percent; metabolic-nutritional, 4.4 percent; central nervous system, 1.5 percent, skin, 1.1 percent; hemic and lymphatic, 0.9 percent; urogenital, 0.8 percent; body as a whole, 0.5 percent; cardiovascular, 0.2 percent; special senses, 0.2 percent; musculoskeletal, 0.1 percent; and respiratory, 0.1 percent. Several patients had more than one reaction. The total incidence of side effects for the treated patients was 9.3 percent. The vast majority of adverse reactions were mild or moderate (94 percent). Serious side effects were reported for 55 patients (6 percent). Based on the 9,473 courses, the incidence of severe reactions was 0.6 percent. Ciprofloxacin treatment was discontinued due to side effects in 146 patients (1.5 percent), mostly due to gastrointestinal reactions (80 patients). The worldwide data from clinical trials with oral ciprofloxacin clearly demonstrate that the drug is relatively safe, and the side effects are usually mild or moderate in intensity and are reversible.

Dados clínicos mundiais sobre a eficácia e a segurança da ciprofloxacina / World wide clinical data on efficacy and safety of ciprofloxacin

Em ensaios clínicos 8.861 pacientes foram tratados com ciprofloxacina a nível mundial. Dos tratamentos realizados,03.822 foram válidos para análise da eficácia, de acordo cocm os padröes do FDA. Em geral foram administradas as seguintes doses: infecçöes do trato urinário: 100 a 50 mg duas vezes por dia, por via oral ou 100 mg duas vezes por dia, por via intravenosa; infecçöes do trato respiratório: 250 a 1.000 mg, duas vezes ao dia, por via oral ou 200 mg duas vezes por dia, por via intravenosa; septicemia: 200 mg duas vezes por dia, por via intravenosa; gonorréia: 250 a 500 mg, por via oral, em dose única; todas as outras infecçöes: 500 a 1000 mg duas vezes por dia, por via oral ou 200 mg, duas vezes por dia, por via intravenosa. A ciprofloxacina foi administrada em 762 tratamentos de infecçöes respiratórias baixas, 88 infecçöes respiratórias altas, 108 bacteremias, 766 infecçöes de pele e anexos, 142 infecçöes dos ossos e articulaçöes, 149 infecçöes intra-abdominais, 33 infecçöes gastrintestinais, 1.633 infecçöes do trato urinário, 49 infecçöes pélvicas, 279 doenças transmitidas sexualmente, principalmente gonorréia, e em três meningites. A resposta clínica foi cura em 76%, melhora em 18% e falha em apenas 6%. A resposta bacteriológica em relaçäo a todos os locais avaliáveis foi: patógenos erradicados em 74%, acentuadamente reduzidos em 2% e persistentes em 10%. Ocorrem recidivas em 4% e reinfecçöes em outros 6%. A resposta global foi favorável em 90% dos pacientes. A segurança da droga foi estabelecida com base nos dados de 8.861 tratamentos a nível mundial. De acordo com a terminologia de COSTART, foram observadas as seguintes reaçöes adversas: digestivas 5%, metabólico-nutricionais 4,6% sistema nervoso central 1,6%, pele 1,4%, hematológicas e linfáticas 1%, cardiovasculares 0,4%, urogenitais 0,3%, órgäos dos sentidos 0,3%, músculo-esqueléticas 0,1%, respiratórias 0,08%...

Clinical experience with ciprofloxacin in the treatment of urinary tract infections: a review.

During the clinical development of ciprofloxacin 1,519 treatments of UTI were documented. The most frequent specific diagnoses were uncomplicated UTI (46.6%), followed by non-specified UTI (21.7%), complicated UTI (19.4%), acute pyelonephritis (7.6%) and chronic pyelonephritis (4.1%). 70% of the causative organisms isolated were Enterobacteriaceae (Escherichia coli 38%, Proteus spp. 10% and Klebsiella pneumoniae 10%). Pseudomonas aeruginosa occurred in approximately 20% of the cases and the remaining 10% were gram-positive aerobes. Clinical resolution was achieved in about 90% in all specific diagnoses. The eradication rate for gram-negative Enterobacteriaceae was 93.8%, for P. aeruginosa 81.8% and for gram-positive aerobes 90.2%. Studies comparing ciprofloxacin and standard treatment have shown the high efficacy of ciprofloxacin making it a preferred agent particularly for infections caused by pathogens less susceptible to conventional drugs. According to the experience of clinical trials the recommended ciprofloxacin dose varies between 100 and 500 mg b.i.d. orally depending on the severity of clinical status and the susceptibility of the pathogen.

Worldwide clinical data on efficacy and safety of ciprofloxacin.

During the clinical trials 8,861 patients have been treated with ciprofloxacin worldwide. 3,822 of the therapeutic courses were valid for analysis of efficacy according to FDA standards. The following dosages were usually administered: UTI: 100 to 500 mg twice daily orally or 100 mg twice daily intravenously; RTI: 250 to 1000 mg twice daily orally or 200 mg twice daily intravenously; septicemia: 200 mg intravenously twice daily; gonorrhea: 250 to 500 mg single tablet orally; all other infections: 500 to 1000 mg twice daily orally or 200 mg twice daily intravenously. Ciprofloxacin was administered to 762 courses of lower RTI, 88 courses of upper RTI, 108 courses of bacteremia, 766 courses of skin structure infection, 142 courses of bone and joint infections, 149 courses of intra-abdominal infections, 33 courses of gastrointestinal infections, 1,633 courses of UTI, 49 courses of pelvic infections, 279 courses of STD, mainly gonorrhea, and three courses of meningitis. The clinical response was resolution in 76%, improvement in 18% and failure in only 6%. Bacteriologic response by all sites evaluable: pathogens were eradicated from 74%, markedly reduced in 2%, persisted in 10%. Relapse occurred in 4% and reinfection was observed in another 6%. The overall response was favourable for 90% of the patients. Drug safety was established on a data base of 8,861 courses worldwide. The following side-effects according to COSTART terminology were observed: digestive 5%, metabolic nutritional 4.6%, central nervous 1.6%, skin 1.4%, hemic and lymphatic 1%, cardiovascular 0.4%, body as a whole 0.4%, urogenital 0.3%, special senses 0.3%, musculo-skeletal 0.1%, respiratory 0.08%. Several courses had more than one reaction. Thus the total incidence of side-effects for the treated patient population was 10.2%. Ciprofloxacin is a highly effective drug and a breakthrough in several areas of medical interest. It is relatively safe and side-effects are usually mild or moderate in intensity and transient.

[Therapy with an antibiotic combination mezlocillin/oxacillin and clinical experience/Second communication: Children (author's transl)]. / Therapie mit Antibiotika-Kombinationen - klinische Erfahrungen mit einer Mezlocillin-Oxacillin-Kombination. 2. Mitteilung: Kinder.

Almost all infections of newborn have to be treated with antibiotics before the result of microbiological examination is available since there are either difficulties in identifying the causative organisms(s) or antibiotic treatment must be instituted without delay in view of the patient's life threatening condition. The present paper reports on the therapeutic results obtained in association with the multicentre study of 51 children affected by bacterial infections. 17 (33.0%) patients were newborn up to one week of age. 12 patients were classified as premature babies, some presenting a high degree of immaturity. Treatment with Optocillin (Bay 1-1330), a combination of 6-((R)-2-[3-Methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido)-penicillanic acid sodium salt (mezlocillin, Baypen) and 5-methyl-3-phenyl-4-isoxazolyl-penicillin (oxacillin, Stapenor), proved effective in 90% of the children, although 22 patients had been treated with other antibiotics prior to the use of this compound. An average daily dose of about 225 mg/kg bodyweight was found to be effective and perfectly tolerated even on long-term treatment, as became evident from two cases of extremely premature babies effected by neonatal septicaemia (duration of treatment 38 and 34 days, respectively). The combination showed a perfect local tolerance, exanthema appearing only in one infant.