Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions.

BACKGROUND: Giardia intestinalis is microaerophilic diarrhoea-causing protozoan common in countries with suboptimal sanitation. Standard treatment is with nitroimidazoles, but a growing number of refractory cases is being reported. Treatment failure has become increasingly prevalent in travellers who contract giardiasis in Asia. Clinicians are increasingly falling back on second-line and less well-known drugs to treat giardiasis. AIMS: To review nitroimidazole-refractory G. intestinalis infection, examine the current efficacy of standard therapeutic agents, consider potential resistance mechanisms which could cause treatment failure and describe the practical aspects of managing this emerging clinical problem. SOURCES: A PubMed search was conducted using combinations of the following terms: refractory, Giardia, giardiasis, resistance and treatment. Articles on the pharmacotherapy, drug resistance mechanisms and use of alternative agents in nitroimidazole-refractory giardiasis were reviewed. CONTENT: We review the standard drugs for giardiasis, including their efficacy in initial treatment, mode of action and documented in vitro and in vivo drug resistance. We assess the efficacy of alternative drugs in nitroimidazole-refractory disease. Existing data suggest a potential advantage of combination treatment. IMPLICATIONS: An optimal treatment strategy for refractory giardiasis has still to be determined, so there is no standard treatment regimen for nitroimidazole-refractory giardiasis. Further work on drug resistance mechanisms and the use of drug combinations in this condition is a priority.

A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children.

OBJECTIVE: To evaluate whether a single dose of intramuscularly administered dexamethasone acetate (IM Dex) was as safe and effective as a 5-day course of oral prednisone (PO Pred) in the treatment of young children with mild-moderate exacerbations of asthma. STUDY DESIGN: A prospective, randomized, investigator-blinded study was done in a tertiary care medical center in children (6 months to 7 years of age) who required corticosteroids to treat mild-moderate asthma exacerbations as outpatients. Patients were randomized to receive either a single dose of IM Dex ( approximately 1.7 mg/kg) or PO Pred ( approximately 2 mg/kg/d for 5 days). Clinical asthma score, behavioral changes, albuterol use, and tolerance of the medication were recorded in a home diary for 7 days. Cortisol/creatinine ratios on first morning void urine samples were obtained on day 14. The primary outcome measures were changes in clinical asthma score through day 5 and tolerance of the medication. RESULTS: Fifteen patients in the IM Dex group (mean age 37 months) and 17 in the PO Pred group (mean age 36 months) completed the study. Clinical asthma score improved significantly in both groups during the first 5 days of therapy, and no significant difference was seen in the rate of improvement between the 2 groups. Three children refused more than 75% of their prednisone doses, and another 4 missed 30% to 50% of the doses despite their parents' best efforts. The intramuscular injection caused no complications, and approximately 70% of parents in both groups stated that they would choose IM Dex to treat their child's next asthma exacerbation. CONCLUSION: In this group of children a single intramuscular injection of dexamethasone acetate was as effective as a 5-day course of PO Pred for the management of mild-moderate outpatient asthma exacerbations.

Allergy history does not predict skin test reactivity in asthmatic children.

We prospectively assessed how well patient report of allergy to cat, dust mite, and grass predicted the results of skin prick testing to those allergens in 95 asthmatic children. Children between 4 and 18 years old with physician-documented asthma provided a detailed standardized allergy history and then underwent skin prick testing. The children were categorized by asthma severity. The diagnostic accuracy, which was the primary outcome measure, as well as sensitivity, specificity, and positive and negative predicted values were calculated for allergy history with regards to skin test reactivity. The diagnostic accuracy of allergy history in identifying skin test reactivity was 65%, 50%, and 56% for cat, dust mite, and grass, respectively. Asthma severity did not affect the diagnostic accuracy. Allergy history was a poor predictor of skin test reactivity in this group of asthmatic children.

Effect of prednisone on response to influenza virus vaccine in asthmatic children.

OBJECTIVE: To evaluate the immunogenicity of the influenza virus vaccine in children receiving short-course (a burst) prednisone therapy for acute asthmatic exacerbations. DESIGN: Prospective cohort study. SETTING: Outpatient pediatric clinic of a military medical center. PATIENTS: Children aged 6 months to 18 years requiring the 1996 influenza virus vaccine were eligible for the study. A total of 58 children were enrolled initially. The control group included 37 asthmatic children requiring less than 900 microg/d of inhaled prednisone and their siblings. The prednisone group included 21 children vaccinated at the beginning of a course of prednisone prescribed to treat an asthma exacerbation. Thirty-one control subjects (84%) and 19 patients in the prednisone group (90%) completed the study. Dropout was due to failure to come in for the postvaccination serum sampling. INTERVENTIONS: All study patients underwent immunization with the 1996-1997 trivalent subvirion influenza virus vaccine (FluShield; Wyeth Laboratories Inc, Marietta, Pa) containing 15-microg hemagglutinin antigens each of A/Texas/36/91 (H1N1) (A/H1), A/Wuhan/359/95 (H3N2)(A/H3), and B/Beijing/184/93 (B). The prednisone cohort received a burst of oral prednisone therapy (2 mg/kg per day for 5 days). MAIN OUTCOME MEASURES: To assess the immunogenicity of the vaccine between both groups, at least a 4-fold rise in titer and end titers of at least 1:40 to each of the 3 antigens were compared. Mean changes in geometric titers to the 3 antigens were also compared. RESULTS: Proportion of patients in each group with at least a 4-fold rise in titer to each of the influenza antigens was as follows: for A/H3N3 antigen, 15 patients (79%) in the prednisone group vs 22 controls (71%) (P = .74); for A/ H1N1 antigen, 16 patients in the prednisone group (84%) vs 20 controls (64%) (P = .20); and for B antigen, 7 patients in the prednisone group (37%) vs 8 controls (26%) (P = .53). Proportion of patients in each group with an end titer of at least 1:40 to each of the antigens was as follows: for A/ H3N2 antigen, 18 patients in the prednisone group (95%) vs 28 controls (90%) (P = .69); for A/H1N1 antigen, 17 patients in the prednisone group (89%) vs 26 controls (84%) (P = .99); and for B antigen, 7 patients in the prednisone group (37%) vs 13 controls (42%) (P = .99). There were also no significant differences between groups in the mean changes in geometric titers to any of the 3 antigens. CONCLUSIONS: Prednisone bursts did not diminish the response of asthmatic children to the 1996 influenza virus vaccine, compared with controls. Children can be effectively vaccinated against influenza virus while they are receiving prednisone therapy bursts for asthmatic exacerbations.

Evaluation of heliox in children hospitalized with acute severe asthma. A randomized crossover trial.

STUDY OBJECTIVE: To determine whether breathing a blend of 70% helium:30% oxygen (heliox) would improve pulmonary function, decrease clinical score, and improve the sensation of dyspnea in children hospitalized with acute severe asthma. DESIGN: Prospective, randomized, double-blind, crossover study. SETTING: The inpatient pediatric service of a military, tertiary care, teaching hospital. PATIENTS: Children 5 to 18 years who required hospital admission for treatment of acute asthma. INTERVENTIONS: All patients received 5 mg of nebulized albuterol every 1 to 4 h, with a dose given within 30 min of the start of the study, and IV administered methylprednisolone. Patients breathed heliox and a 30% oxygen-enriched air mixture for 15 min each in random order. MEASUREMENTS AND RESULTS: Clinical score, dyspnea score, oxygen saturation, heart rate, and respiratory rate, followed by FVC, FEV1, peak expiratory flow rate (PEFR), and, mean midexpiratory flow rate (FEF25-75) were obtained at study entry, 15 min after breathing the first gas mixture (heliox or air per randomization), 15 min after breathing the second mixture, and again 15 min after stopping the second gas mixture (study end values). Eleven children were enrolled, and all completed the study. There were no significant differences between study entry and study end spirometric values. Using the paired t test, we found no significant differences between mean values (SD) of FEV1 and FVC obtained while breathing heliox vs air; FEV1-heliox, 53% (18%) of the predicted value; FEV1-air, 52% (16%) of the predicted value (p = 0.36); FVC-heliox, 69% (22%) of the predicted value; and FVC-air, 70% (21%) of the predicted value (p = 0.50). The differences in values for PEFSR and FEF25-75 while breathing heliox vs air were small but did reach statistical significance in favor of heliox: PEFR-heliox, 56% (20%) of the predicted value; PEFR-air, 50% (16%) of the predicted value (p = 0.04); FEF25-75-heliox, 32% (13%) of the predicted value; and FEF25-75-heliox, 29% (11%) of the predicted value (p = 0.006). Heliox had no effect on either clinical or dyspnea scores. CONCLUSION: The short-term inhalation of heliox did not benefit this group of children hospitalized with acute, severe asthma.

Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress.

PURPOSE: To evaluate the effects of a new microbubble contrast agent for ultrasound (US) on breast masses. MATERIALS AND METHODS: Thirty-four patients underwent color Doppler US before and after intravenous injection of a "contrast agent" containing microbubbles. The authors subjectively evaluated the increase in intensity of the Doppler signals, the changes in the vascular patterns, and the timing of the transit of the microbubble bolus. The diagnostic confidence was assessed before and after administration of contrast material. RESULTS: After contrast material injection, there was greater and longer signal enhancement in the cancers than in the benign lesions. The cancers displayed characteristic vascular morphologic features, with more additional vessels visualized in relation to the lesion and a greater increase in vascular tortuousity. Shunts between vessels were demonstrated in all cancers but were not seen in any benign lesion. The diagnostic confidence increased with use of the contrast agent. The appearance at contrast-enhanced US led to a change in the US diagnosis in four patients. This increased both sensitivity and specificity to 100%. CONCLUSION: Injection of a microbubble agent enabled accurate differentiation of benign masses from carcinomas.