Pharmacokinetics of two dosage regimens of ciprofloxacin during a two-week therapeutic trial in patients with cystic fibrosis.

Twenty-nine adult patients with cystic fibrosis received 750 or 1,000 mg of ciprofloxacin orally every 12 hours for two weeks. Pharmacokinetic data were collected on Days 1, 7, and 14. Pharmacokinetic analyses revealed minor differences between the dosage regimens, and results were similar on the first, seventh, and last day of therapy. Means for peak serum concentration (3.1 to 5.0 micrograms/ml), elimination half-life (4.8 to 5.3 hours), area under the time-concentration curve, and serum clearance (36.8 to 44.5 liter/hour) were similar to previously reported results for patients without cystic fibrosis. Sputum concentrations approximated serum values.

Randomized study of two dosage regimens of ciprofloxacin for treating chronic bronchopulmonary infection in patients with cystic fibrosis.

Twenty-nine adult patients with cystic fibrosis who had chronic bronchopulmonary infection were randomly assigned to receive 750 or 1,000 mg of oral ciprofloxacin every 12 hours for two weeks. Assessments for efficacy and safety were made on treatment Days 7 and 14 and one week following completion of therapy, and pharmacokinetic data were collected on Days 1, 7, and 14. Fifteen of 28 evaluable patients showed clinical improvement, and none had clinical deterioration. The higher dosage of ciprofloxacin did not enhance the clinical response. Statistically significant, stepwise changes in clinical scores, pulmonary function, and sputum concentrations of Pseudomonas aeruginosa and Staphylococcus aureus were noted, but regression toward initial values occurred by one week after treatment. Although all P. aeruginosa isolates were initially inhibited by 2 mg/liter of ciprofloxacin or less, 45 and 35 percent of isolates were resistant after 14 days of therapy and one week later, respectively. Outpatient oral ciprofloxacin therapy was commonly associated with clinical improvement in adult patients with cystic fibrosis who have chronic bronchopulmonary infection, regardless of the emergence of resistant P. aeruginosa, and adverse reactions were infrequent. Further studies must delineate the long-term consequences of the frequent emergence of bacterial resistance.

Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences.

The excretion of drugs in human breast milk is reviewed with regard to milk production, composition, feeding patterns and mechanisms of drug transfer into milk. Fundamental principles of breast milk excretion are used to construct a pharmacokinetic approach useful for the study of most drugs. An infant-modulated 3-compartment open model is proposed for drug distribution and elimination in the breast feeding woman. Milk/plasma drug concentration ratios are projected on the basis of pH partitioning. While some studies confirm these projections, other studies demonstrate a need to consider additional factors such as lipid solubility and protein binding characteristics of a drug in milk. Data are lacking for most drugs and hence dosing via milk or risk to the infant remains speculative. Very few pharmacokinetic studies of both milk and infant plasma were found. A review of selected drug classes cites available information as a basis for future studies. Few drugs are contraindicated in breast feeding women, but supportive data for either proscriptions or permissive statements are often lacking. A neglected but potentially serious infant risk--impaired behaviour and development--is discussed from the standpoint of emerging animal data. Conceptually valid and comprehensive studies on drug excretion in breast milk are needed if this valuable nutrient for infants is to be made available safely.

Foreign body aspiration of grass inflorescences as a cause of hemoptysis.

Although the sparsity of reports in the literature suggest aspiration of grass inflorescence is rare, in certain areas of the southern United States, aspiration of this type of foreign body is not so uncommon. Four cases of aspiration of Hordeum pusillium, often referred to as "cheat grass" are reported: three of the four patients had hemoptysis. The highest incidence of inhaled foreign bodies usually occur in young children, but all our four patients were older children or adolescents. The clinical manifestations of grass inflorescence are of the following two types: (1) the "lodging" type in which inflorescences remain in the respiratory passages causing bronchial obstruction with pneumonitis; and (2) the "extrusive type" in which the inflorescences migrate into the periphery of the lung and through the chest wall.

Comparison of two selective media developed to isolate Pseudomonas cepacia from patients with cystic fibrosis.

Two media selective for Pseudomonas cepacia have been described recently: OF-polymyxinbacitracin-lactose agar (OFPBL) and P. cepacia agar (PCA). We compared these by culturing sputum from 27 patients with cystic fibrosis. Sputum from each patient was studied using streak-plate (SP) and quantitative (Q) culture methods. Five strains of P. cepacia were isolated from four patients (15%). P. cepacia was not found on routine media by SP or Q methods in three of the four patients. All five isolates grew on both OFPBL and PCA and all were recovered by SP and Q culture methods. Colony counts of P. cepacia obtained by Q cultures were similar on both selective media. Each of the selective media allowed the growth of other organisms; nineteen of 27 specimens cultured on OFPBL yielded non-P. cepacia spp. and six of 27 specimens cultured on PCA yielded non-P. cepacia spp. species (p less than 0.005). Pseudomonas aeruginosa was isolated from 26 of 27 patients on routine media (96%). This organism was recovered from four specimens cultured on OFPBL but from none on PCA (p less than 0.05). OFPBL and PCA are both selective for P. cepacia and enhance the ability to recover this organism from patients with cystic fibrosis using either SP or Q cultures of sputum; however, PCA is significantly more inhibitory for non-P. cepacia spp. than OFPBL.

Resting energy expenditures measured by indirect calorimetry are higher in preadolescent children with cystic fibrosis than expenditures calculated from prediction equations.

OBJECTIVE: This study compared measured resting energy expenditures to resting energy expenditures calculated using Harris-Benedict equations (HBEs) and the Cystic Fibrosis Consensus Committee equations (CFCCEs). DESIGN: We studied 31 preadolescent boys and girls with cystic fibrosis who ranged in age from 3.25 to 12.75 years old. The patients were afebrile and not in pulmonary distress. Measured resting energy expenditures were determined using a portable metabolic measurement cart with fully automated calibration and data management. The measured resting energy expenditures obtained were compared with values obtained using HBEs and CFCCEs. RESULTS: For each patient, the measured resting energy expenditure value was above the predicted resting energy expenditure values derived from HBEs (P < or = .0001) and CFCCEs (P < or = .01). APPLICATIONS: The HBEs and the CFCCEs underestimated the energy expenditures of the study population by 13% and 8%, respectively. These findings support the usefulness of the measurement of energy expenditures in determining the energy needs of preadolescent patients with cystic fibrosis. In clinical practice, the resting energy expenditures would be multiplied by activity coefficients to determine the total daily energy expenditures of this population.

Interstitial lung disease in children.

Interstitial lung disease in children is a heterogeneous group of disorders of both known and unknown causes that share a common histologic characteristic (i.e., inflammation of the pulmonary interstitium that may resolve completely, partially, or progress to derangement of alveolar structures with varying degrees of fibrosis). The inflammatory process, evoked as a result of injury to alveolar epithelium and/or the endothelium, is responsible for alveolar wall thickening that is the histologic marker of ILD. This article extrapolates some of the known pathogenic mechanisms of ILD from adult and animal models and applies this information for a better understanding of the pathogenesis of ILD in children. The clinical manifestations vary and are often subtle and nonspecific. There is no consensus on specific criteria for the clinical diagnosis of ILD in children. There are no pathognomonic laboratory criteria for the diagnosis of ILD in children other than the characteristic findings on histologic examination of the lung. It is important to make the diagnosis early to minimize lung damage. Therapy is directed toward the reduction of the inflammatory response to minimize or prevent the progression to fibrosis. ILD suffers from lack of uniform guidelines for diagnostic evaluation, therapy, and prognostic indicators essential for critical monitoring of disease activity. No one medical center has enough cases of ILD in children to allow objective evaluation of a significant number of cases with adequate longitudinal follow-up to determine guidelines for optimal management and to identify accurate prognostic indicators. The organization of a multicenter approach will guide us towards a better understanding of ILD in children.

Successful prenatal management of hydrops, caused by congenital cystic adenomatoid malformation, using serial aspirations.

Congenital cystic adenomatoid malformation (CCAM) is a lung lesion that is now commonly diagnosed in utero with fetal ultrasonography. The described treatment of this lesion includes observation with treatment delivery, a single aspiration, thoraco-amniotic shunts, and fetal resection. This patient had an in utero diagnosis of a Stocker type I CCAM associated with hydrops. Fetal resection was not an option because of patient refusal. The fetus was treated with multiple serial aspirations. There was marked improvement of the anasarca, and subsequently the baby was born without respiratory distress. On the second day of life the CCAM began to expand, and the right lower lobe was resected. The baby's postoperative course was uneventful. CCAM with hydrops is associated with a high mortality rate. Current recommended therapy for these lesions is fetal resection or thoracoamniotic shunt. The authors' patient was treated with serial fetal thoracocenteses, with an excellent outcome. This therapy may be an alternative to fetal surgery or an adjunct to fetal surgery in selected cases.

Pediatric tuberculosis: problems in diagnosis and issues in management.

The diagnosis of infection and disease due to Mycobacterium tuberculosis in infants and children presents many clinical challenges. The distinction of infection from disease (tuberculosis) in children is often unclear. There is difficulty in obtaining positive microbiological confirmation of infection in sputum, gastric, tracheal, or bronchial aspirates and in other body fluids in infants and children. Isoniazid is effective in the treatment of infection and prevention of progression of infection to clinical disease. Approximately 50% of children with primary tuberculosis are asymptomatic and are diagnosed as a result of contact investigation. Children become infected from exposure to an adult or adolescent with contagious pulmonary tuberculosis. The results of drug susceptibility tests in the source case in contact with an exposed child can guide the antituberculous chemotherapy. Chemotherapy regimens for treatment of pediatric tuberculosis have become shorter and more intensive with a marked increase in directly observed therapy (DOT).

Evaluation of the wheezing infant.

Wheezing is a very common symptom or sign in the infant. The evaluation of the underlying cause of the wheezing is difficult and requires a thorough assessment of several factors in the history and physical examination and a basic understanding of the pathophysiology of wheezing. With the increased availability of infant pulmonary function equipment, the evaluation of serial pulmonary function studies in infants with wheezing should prove helpful in continued assessment of the reversibility of their airway obstruction using bronchodilators and the effect of antiinflammatory pharmacologic agents on long-term hyperresponsiveness of the airways. Wheezing-associated respiratory tract infections in infancy ("wheezy bronchitis") and asthma share common risk factors, including history of exposure to environmental tobacco smoke, but the link between these two entities is still controversial. Each infant who presents with wheezing should be assessed individually with a thorough history and physical examination and an evaluation of the likelihood of asthma versus other underlying causes of wheezing such as cystic fibrosis, aspiration syndromes, congenital anomalies, or environmental factors such as exposure to passive tobacco smoking.

Genetic and immunologic aspects of cystic fibrosis.

LEARNING OBJECTIVES: Reading this article will enable the readers to reinforce their knowledge of the pathophysiology of cystic fibrosis (CF), the pathogenesis of the lung disease, the criteria for diagnosis, and CF genotype/phenotype relationships. The focus of this review is on the genetic and immunologic aspects of CF. DATA SOURCE: Relevant articles, current texts, data presented at the annual North American Cystic Fibrosis Conferences and distributed to the Directors of CF Centers by the CF Foundation were reviewed. A MEDLINE database using subject keywords was searched from 1987 to date. Background information derived from the author's 33 years of clinical experience at three of the CF Foundation's CF Care, Teaching and Resource Centers was also included. STUDY SELECTION: Since CF is an inherited disorder, the genetic aspects are emphasized. With the cloning of the CF gene, DNA analysis has assumed an important role in confirming the clinical diagnosis and in the improved understanding of the pathophysiology of this disorder. Although DNA testing is highly specific, it is not very sensitive. RESULTS: Cystic fibrosis gene structure and function are described briefly. The pathophysiology of CF, as it relates to the CF gene defect, and the current knowledge of the pathogenesis of the lung disease are reviewed. The criteria for the diagnosis proposed by the Clinical Practice Guidelines for CF are discussed. Problems of establishing the diagnosis and the importance of correlations of laboratory and clinical findings in CF are emphasized. CONCLUSIONS: As a multisystem disorder, CF can masquerade as other disorders, including allergic respiratory disease. Primary care physicians often refer patients to allergists/immunologists because of recurrent respiratory problems. This review discusses the genetic heterogeneity of CF.

Cystic fibrosis--a challenging masquerader.

CF, a generalized dysfunction of the exocrine glands, is an inherited disorder with variable clinical manifestations and prognosis. Because of the multisystem involvement, CF can masquerade as other disorders, including allergy. A high index of suspicion and a knowledge of the variable manifestations of this complex multisystem syndrome are essential for early diagnosis of this challenging masquerader. Quantitative analysis of sweat electrolyte levels after pilocarpine iontophoresis is the cornerstone of the diagnosis of CF. Because respiratory involvement causes most of the morbidity and mortality, aggressive treatment of pulmonary infection and efforts to reduce obstruction of the airways are essential in the treatment of CF. Until the basic defect that causes CF is identified, control or stabilization of the disease and management of its complications, rather than a cure, are the realistic goals of treatment. A comprehensive approach to management includes education of the patient about the disease and its treatment, supportive counseling, dietary supplementation, and aggressive therapy for pulmonary disease.

Normal values for forced oscillation parameters in small children.

A commercially available forced oscillation unit was used to perform pulmonary function testing in 90 healthy children, aged 4 to 7 years. Normal values for resistance and reactance of the respiratory system, resonant frequency, and frequency dependence are reported. The implications of each of the forced oscillation parameters, and their potential usefulness as objective measures of pulmonary function in young children, are discussed.

Management options: SCIDS with adenosine deaminase deficiency.

Of the currently available options for the treatment of ADA deficiency, the treatment of choice remains transplantation of bone marrow from an HLA identical donor. When an HLA-identical donor is not available, haploidentical BMT or enzyme replacement needs to be considered and evaluated on an individual basis. Haploidentical BMT may be potentially curative, but this form of therapy is not without risks, especially in severely ill patients or in patients requiring cytoablation. The ability to utilize PEG-ADA even in ill patients, is certainly an advantage over haploidentical BMT. Polyethylene glycol-adenosine deaminase enzyme replacement usually entails a shorter time of hospitalization, but is very expensive for long-term treatment. The expense will increase as the patient requires higher doses of the enzyme replacement with increasing weight. Although PEG-ADA enzyme replacement therapy has been shown to be effective without significant risks to patients with SCIDS, there is increasing concern that this form of therapy may be jeopardized due to expense for long-term treatment in the current era of managed care and health care reforms. The use of PEG-ADA enzyme replacement is associated with decreased morbidity and mortality when compared with haploidentical BMT transplantation. There have been only two deaths among the 29 patients treated with PEG-ADA. In contrast, the 2-year survival for BMT in ADA deficient patients is quite variable ranging from 0% to 66%.(ABSTRACT TRUNCATED AT 400 WORDS)