zithromax and Hypertrophy

The safety profile of erythromycin is notable for the frequent occurrence of intolerable gastrointestinal effects. One of the more serious of these is infantile hypertrophic pyloric stenosis (IHPS). A recent cluster of IHPS cases prompted an epidemiological investigation which identified oral erythromycin chemoprophylaxis of pertussis as the major risk factor. Evidence suggests an association between early postnatal erythromycin exposure and IHPS. There is no substantive evidence of a risk associated with prenatal exposure, with the single published case-control study to date producing negative findings. The epidemiological investigations of the association with early postnatal exposure have reported significantly elevated odds ratios but have a variety of methodological limitations that prevent definitive conclusions being made. Nevertheless, the concordance of findings across studies increases the strength of evidence favouring an association. The prominent gastrokinetic properties of erythromycin have been postulated as the mechanism behind this phenomenon. A comprehensive assessment of this potential adverse effect should consider its biological plausibility in light of known gastrointestinal physiology, its modulation by erythromycin, and the known pathophysiology of IHPS. Gastrointestinal motor activity in the fasted mammal consists of three phases, phase III being large amplitude contractions called migrating motor complexes (MMC) that can be initiated by motilin and erythromycin. The gastrokinetic effects of erythromycin are variable and complex and include effects on the timing, duration, amplitude and distribution of MMCs. It has been speculated that the motilinomimetic effects of erythromycin on antral smooth muscle function, such as the MMC, may mediate the effect via work hypertrophy. Although intuitively plausible and consistent with hypertrophic obstructive changes similar to IHPS observed in hyperplastic rat ileum after artificially induced mechanical obstruction, there is no direct evidence of this phenomenon. Further complicating the association is the limitations of our knowledge about the pathophysiology of IHPS, including numerous genetic abnormalities, increased parietal cell mass, and gastric hyperacidity. The implications of the reported findings with erythromycin on the benefit-risk profiles of newer macrolides and azalides must be considered. The available data on the comparative gastrokinetic properties of macrolides are signifi

Topics: Adverse Drug Reaction Reporting Systems; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Cohort Studies; Databases, Factual; Digestive System; Erythromycin; Female; Gastrointestinal Motility; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Pyloric Stenosis; Retrospective Studies

Multiple clinical trials demonstrate the value of administering antibiotics for recurrent tonsillitis. However, there is no consensus as to the role of antibiotics in the management of adenotonsillar hypertrophy and obstructive sleep apnea (OSA). It has been suggested that antibiotics may reduce adenotonsillar size, improve obstructive symptoms, and obviate the need for surgery. The goal of this pilot study was to evaluate the efficacy of a broad-spectrum antibiotic in the management of adenotonsillar hypertrophy and OSA.. Twenty-two children ages 2 through 12, with evidence of OSA, were enrolled in this double-blinded, prospective clinical trial. Children were randomly assigned into 1 of 2 groups. Group I received azithromycin for a 30-day period (12 mg/kg on days 1-5; the regimen was repeated on days 11-15 and days 21-25). Group II received a placebo administered in the same regimen for a 30-day period. Overnight polysomnography was performed before and within 2 weeks after drug administration.. Polysomnographic indices of OSA severity appear to indicate an improvement in the antibiotic as compared to the placebo group, but a comparison of mean +/- standard error for each parameter failed to demonstrate statistical significance using the paired t test. Only 1 of 11 (9%) children had normalization of their polysomnographic parameters.. These results suggest that a course of a broad-spectrum antibiotic may be effective in temporarily improving OSA due to adenotonsillar hypertrophy, but does not appear to obviate the need for surgery.

Topics: Adenoids; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Double-Blind Method; Female; Humans; Hypertrophy; Male; Palatine Tonsil; Pilot Projects; Polysomnography; Prospective Studies; Severity of Illness Index; Sleep Apnea, Obstructive; Treatment Outcome

This study was performed in children with adenotonsillar hypertrophy to evaluate the effect of azithromycin (AZT) on the presence of NTHi in monocyte/macrophages (CD14(+) cells) of adenoids/tonsils and the persistence of NTHi after adenotonsillectomy. A total of 36 pediatric patients participated in the study: 20 children were treated with AZT before adenotonsillectomy, and 16 children did not receive the antibiotic prior to surgery. NTHi were identified by culture and PCR in swabs and tissue samples. NTHi was detected in the lysates of CD14(+) cells by fluorescence in situ hybridization (FISH) and by culture. The molecular typing was used to cluster NTHi isolates from each child. The intracellular NTHi was found in 10 (62.5%) untreated patients and was identified in three (15%) azithromycin-treated patients (P = 0.003). The proportion of the persistent NTHi strains was similar in both groups. AZT treatment followed by adenotonsillectomy did not completely eliminate NTHi from pharynges; however, it significantly reduced the risk of carriage of Haemophilus influenzae inside the CD14(+) cells.

Topics: Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Hypertrophy; Lymph Nodes; Male; Molecular Typing; Palatine Tonsil; Pharynx; Prospective Studies