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.

Antibiotic cover of transurethral maneuvers with ciprofloxacin and susceptibility behavior of pathogens in patients with neurogenic bladder.

The resistance-inducing capacity of ciprofloxacin is still controversial. In order to assess the changes in susceptibility behavior, ciprofloxacin was given as antibiotic cover for transurethral maneuvers in multiple sclerosis (MS) patients with urinary tract infection prone to recurrence after treatment. The aim was to compare the susceptibility pattern before and after treatment in a double-blind study using two different dose regimens. Sixty-one patients were randomly separated in two groups who received 100 and 500 mg ciprofloxacin orally, twice a day for 4 days. Bacterial cultures were performed before and at the fourth day of treatment as well as at 6 days and 4 weeks after the end of treatment. Altered susceptibility behavior, defined as an elevation of the primary minimum inhibitory concentration by at least two dilution steps, was only found in three causative organisms out of 86, demonstrating the low resistance-inducing capacity of ciprofloxacin. There was no significant dosage-related difference.

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.

Is pelvic inflammatory disease an indication for treatment with ciprofloxacin?

This pilot study was carried out on 23 gynaecological patients suffering from salpingitis, salpingitis and pelviperitonitis, Douglas' abscess, and vaginal stump abscess. 21 courses were evaluable for clinical efficacy. The diagnoses had been established mainly by pelviscopy and by clinical gynaecological examinations. The dosage was 2 X 500 mg ciprofloxacin orally every 12 h for 7.6 (5-11) days. Cervical smears collected before therapy revealed the most common pathogens to be Escherichia coli and staphylococci, followed by Proteus mirabilis and streptococci. Clinically ciprofloxacin produced a complete cure in 16 patients (76%), and a clear improvement in four patients (19%). One patient left hospital before completing the therapy. Laboratory tests did not reveal any pathological findings, and ophthalmological examinations (fundoscopy, visus, colour perception) on 16 patients, before and after treatment, likewise did not show any changes. In one patient, therapy had to be discontinued after three days because of pruritic exanthema and vertigo. A second patient complained of strong pain behind the eyes and headache. In both patients these symptoms disappeared completely on discontinuation of treatment. The study showed clinical efficacy of orally administered ciprofloxacin in pelvic inflammatory disease.

Oral treatment of Pseudomonas-induced urinary tract infections with ciprofloxacin.

In an open study, a group of 11 patients with asymptomatic urinary tract infections, caused by resistant Pseudomonas strains, were given 200 mg of ciprofloxacin per day for 1 week. All strains displayed an in vitro sensitivity to the drug. Complete clinical resolution was obtained in 8 patients and long-term eradication in 3. No adverse reactions and only minor and reversible laboratory changes were recorded. Ciprofloxacin could be a valuable oral drug in the treatment of severe urinary infections. However, more clinical studies on the development of resistance under therapy and with other dose schedules are indicated.

[Mezlocillin and oxacillin concentrations in the bile of the choledochus]. / Mezlocillin- und Oxacillin-Konzentrationen in der Galle des Ductus choledochus.

The purpose of this study was to determine the antibiotic concentrations in serum and bile one and two hours after the completion of a simultaneous short-term infusion of 4 g mezlocillin and 2 g oxacillin. Seven patients were studied. Bile was withdrawn from the bile duct by means of a Teflon catheter. The mean serum concentrations of mezlocillin were 130.4 mg/l and 60.8 mg/l one and two hours after the end of the infusion, respectively. The mean serum concentrations of oxacillin determined at the same times were 57.9 mg/l and 18.9 mg/l, respectively. The mean biliary levels of mezlocillin were 3215.6 mg/l and 2483.1 mg/l one and two hours after the end of the infusion, respectively. The corresponding mean biliary values for oxacillin were 497.3 mg/l and 205.5 mg/l.

Antibiotic concentrations in blood and tissue. Intraoperative ischemia as a model for the determination of tissue concentrations using mezlocillin and oxacillin as examples.

Blood present in the tissue distorts the results obtained during measurement of antibiotic tissue levels. The greater the blood supply to the tissue, the bigger the error when tissue levels are measured. The examination of tissue removed during temporary intraoperative ischemia is an alternative to the indirect mathematical method of correcting errors of blood level measurement. This technique was tested by determining tissue concentrations after i.v. injection of 4 g mezlocillin and 2 g oxacillin. The tissue was removed during operations on limbs after the application of an Esmarch's bandage. Determination of hemoglobin in ischemic tissue confirmed exsanguination so that the 6-((R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenylacetamido )-penicillanic acid-Na (mezlocillin) and 5-methyl-3-phenyl-4-isoxazolylpenicillin (oxacillin) concentrations determined corresponded to the actual tissue levels. The concentrations of mezlocillin and oxacillin in fat, skin, tendon, muscle, ganglion, aponeurosis, tumour, ligament, subcutis, synovial fluid, epineurium and serum are given in the text.

[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.