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Biomedical subjects

J C Craft

Publications and source records attributed to J C Craft.

30 records · Page 2Linked to original sources

Comparison of piperacillin alone versus piperacillin plus tobramycin for treatment of respiratory infections in children with cystic fibrosis.

Seventeen patients with cystic fibrosis (CF) and pulmonary exacerbations were randomly assigned to two treatment groups: piperacillin 600 mg/kg/day (P), and piperacillin 600 mg/kg/day plus tobramycin (PT), in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections. The mean half-life of piperacillin was 0.54 hours, with a peak concentration of 232 micrograms/ml. No differences between P and PT groups were noted in clinical assessment, as judged by Shwachman scores, pulmonary function testing, or weight gain. However, during the course of treatment, quantitative sputum cultures decreased by greater than 10(2) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group, compared with 12 of 19 isolates from the PT group (P less than 0.03, Chi-square). Although emergence of resistance was not seen, one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml. There were no serious adverse reactions to piperacillin; only one patient developed fever possibly related to piperacillin. Therapy with high-dose piperacillin was safe in children with CF. Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum. However, the role of antimicrobial agents in the treatment of CF remains undefined. A double-blind placebo-controlled trial is indicated.

Child↗

Prevalence of giardiasis in patients with cystic fibrosis.

A group of 107 patients with cystic fibrosis and a control group of 64 normal members of households of patients with cystic fibrosis were surveyed for Giardia lamblia cysts and trophozoites by counterimmunoelectrophoresis of fecal samples. The patient group had a significantly higher rate of infestation than the control group (28.0% vs 6.3%, P = 0.0006), and the disparity between the two groups increased with age (P = 0.005). Aside from cystic fibrosis, all risk factors examined were without influence, except for the presence of household members less than or equal to 5 years of age. We conclude that our patients with cystic fibrosis have a previously unrecognized increased prevalence of giardiasis compared with that in a control population.

Adolescent↗

Malabsorption of oral antibiotics in humans and rats with giardiasis.

We observed unexplained treatment failures in 13 patients with serious infections and apparent incidental giardiasis. Antibiotic concentrations were assayed in the serum from patients before initiating anti-Giardia therapy and again 2 to 3 weeks after therapy. The peak serum concentrations of antibiotics were higher after treatment for giardiasis. The rat model of giardiasis was used to examine the hypothesis that oral antibiotics are malabsorbed during Giardia lamblia infection. Twenty-eight-day-old Sprague-Dawley rats were fed amoxicillin (50 mg/kg/dose), ampicillin (50 mg/kg/dose), cefaclor (50 mg/kg/dose), cephalexin (50 mg/kg/dose), erythromycin (50 mg/kg/dose), penicillin V (50 mg/kg/dose) or sulfamethoxazole (20 mg/kg/dose) and sera were assayed for antibiotics at 1, 2, 4, 6 and 12 hours after therapy. The same rats were fed 10(5) G. lamblia cysts on 4 consecutive days. On Day 7 of infection the rats were fed the same antibiotic and sera were assayed for antibiotics at 1, 2, 4, 6 and 12 hours after therapy. The mean peak serum concentrations for all drugs except sulfamethoxazole were significantly higher in the rats before infection with G. lamblia. These data suggest that oral antibiotic therapy maybe compromised by decreased absorption in the presence of giardiasis.

Administration, Oral↗

Experimental infection with Giardia lamblia in rats.

Sprague-Dawley rats were orally inoculated with Giardia lamblia cysts. Infection was documented using microscopic examination of feces, counterimmunoelectrophoresis (CIE) of feces for G. lamblia antigen, and intestinal biopsy. After inoculation with 150 cysts, 100% of the rats became infected. CIE and intestinal biopsy detected infection on days 2-3 after inoculation. Results of microscopic examinations were variable, but cysts were observed as early as day 4. CIE and intestinal biopsy were comparable in detecting infection. The infection rate peaked at day 7 and remained high until day 20. Spontaneous resolution of infection occurred after 28-42 days in 96% of the rats. Cysts stored in liquefied feces at 4 C demonstrated a gradual decline of infectivity but remained infective for one year.

Animals↗

Diagnosis of giardiasis by counterimmunoelectrophoresis of feces.

The diagnosis of giardiasis is frequently difficult. In the present study, the techniques of microscopic examination of feces, duodenal fluid, and duodenal biopsy specimens were compared with counterimmunoelectrophoresis (CIE) of feces for Giardia lamblia antigen. New Zealand white rabbits were immunized with purified G. lamblia cysts and axial trophozoites, and the resulting antiserum was used for the detection of antigen. Of 276 patients with acute and chronic diarrhea studied using standard diagnostic methods, 66 patients had giardiasis: 62 by examination of feces; three, of duodenal fluid, and one, of duodenal biopsy specimens. CIE tests for G. lamblia fecal antigen had positive results for 65 of the 66 patients. The CIE test for Giardia fecal antigen appears to be as sensitive and reliable as the combined examination of feces and duodenal fluid.

Antigens↗

Furazolidone and quinacrine. Comparative study of therapy for giardiasis in children.

Furazolidone and quinacrine hydrochloride were compared for efficacy, toxicity, and ease of administration in 45 young children with giardiasis. With the initial course of therapy, the cure rate was 89% (17/19) with furazolidone and with quinacrine it was 64% (9/14) in children less than 5 years and 92% (11/12) in older children. Cure rates for all courses of therapy were 92% (24/26) with furazolidone and 53% (9/17) and 92% (12/13) in the younger and older children, respectively, treated with quinacrine. Quinacrine failure was usually due to severe vomiting. When re-treated with furazolidone, patients were cured. The disadvantages of furazolidone are the large volume of doses and the expense. In this study, furazolidone was more effective and better tolerated than quinacrine for the treatment of giardiasis.

Adolescent↗

Monitoring antibiotic therapy in the newborn infant.

With antibiotic monitoring, antimicrobial therapy of the neonate can be safe and effective. During this period of transition, the pharmacokinetics of the infant is constantly in a state of flux. Treatment guidelines based on average pharmacokinetics do not always correspond to the values obtained from an individual infant. Individualization of therapy is the goal of monitoring antibiotic therapy in the newborn infant. The MIC and MBC data obtained from susceptibility testing are used to select the most appropriate antibiotic(s). The expected serum antimicrobial concentration should exceed the MIC and MBC by one to five times. Microbiologic, radioenzymatic, radioimmunoassay, high performance liquid chromatography, and other assay methods are currently available in the clinical laboratory. Adjustments of antimicrobial therapy are based on the information provided from assays of peak and trough serum concentration. Bactericidal titers indirectly provide similar information and are adequate for assessing therapy. Indications for monitoring antibiotic therapy in the newborn are dependent on the drug and clinical situation. Aminoglycoside and chloramphenicol, both of which have narrow ranges of serum concentration between efficacy and toxicity, require monitoring. Infants with serious or unusual infections benefit from assays of antibiotics. Other indications for monitoring antimicrobial concentrations are changes in methods of administration, multiple drug therapy, errors in medication, and any situation in which the information can be used to insure efficacy and safety.

Aminoglycosides↗

Cutaneous necrosis associated with intravenous nafcillin therapy.

Four children had cutaneous necrosis associated with the administration of intravenous (IV) nafcillin sodium therapy. One patient required skin grafting. Hospitalization was prolonged with this patient and with one other in an effort to ensure healing. Adult rats, inoculated subcutaneously with nafcillin that was appropriately diluted according to manufacturer's recommendations, exhibited similar lesions. Oxacillin sodium, methicillin sodium, and cephalothin sodium, similarly diluted, did not necrose skin. Nafcillin should be added to the list of agents that produce similar toxic conditions. Frequent observation of the IV infusion site to detect extravasation may obviate this hazard.

Animals↗

Clinicopharmacological evaluation of amoxicillin and probenecid against bacterial meningitis.

Forty-three infants and children with bacterial meningitis were treated intravenously with 200 mg of amoxicillin sodium per kg per day for 10 days. (Patients were initially treated with ampicillin and chloramphenicol until the bacterial etiology was defined.) Patients were randomly treated with amoxicillin only or with amoxicillin and four doses of probenecid (10 mg/kg per dose) orally every 6 h for 24 h before the lumbar puncture at day 10. Serum and cerebrospinal fluid (CSF) were obtained on days 1, 5, and 10 of therapy for antibiotic assay. The mean peak serum concentration of amoxicillin of 49.2 micrograms/ml was increased to 61.4 micrograms/ml in patients who received probenecid. The half-life in serum (1.5 h) and area under the curve with probenecid (112.5 micrograms/ml-h) were increased compared with those of amoxicillin alone (1.3 h and 82.2 micrograms/ml-h). The mean peak CSF concentrations on days 1 and 5 were similar, but day 1 concentrations remained between 2.0 micrograms/ml and 5.0 micrograms/ml throughout the 4 h after a dose, whereas the day 5 values decreased at the same decay rate as that in serum. All CSF concentrations were lower on day 10, but patients receiving probenecid had peak values occurring at 1 hr rather than at 0.5 h, and levels were significantly greater at 1 and 2 h after a dose. There were no deaths and patients responded well to treatment.

Amoxicillin↗