The present results indicate a marked penetration of azithromycin into both normal and pathological periodontal tissues, suggesting that azithromycin represents a promising option in both adjunctive and prophylactic treatments of chronic inflammatory periodontal diseases.
The tissue penetration of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients undergoing surgery for third-molar removal. Drug concentrations in plasma, saliva, and periodontal tissues were evaluated in 28 patients treated with azithromycin 500 mg/day per os for 3 consecutive days. Samples of blood, saliva, gingiva, and alveolar bone were collected during oral surgery, 12 hours, and 2.5, 4.5, and 6.5 days after the last dosing, and the azithromycin concentration was measured microbiologically by using Micrococcus luteus NCTC 8440 as the reference organism. The highest concentrations of azithromycin were observed 12 hours after the last dose in plasma, saliva, gingiva, and bone (0.33 +/- 0.04 mg/l, 2.14 +/- 0.30 mg/l, 6.47 +/- 0.57 mg/kg, and 1.86 +/- 0.15 mg/kg, respectively) and then declined gradually. However, consistent levels of the drug in saliva and periodontal tissues could be detected up to 6.5 days, indicating that azithromycin was retained in target tissues and fluids for a long time after the end of treatment. Among the samples examined, the highest concentration of azithromycin was found in the gingiva at each time studied. Moreover, the ratios of salivary or periodontal tissue levels versus plasma concentrations remained nearly unmodified from 12 hours up to 6.5 days. Overall, these results indicate a favorable disposition of azithromycin into saliva and periodontal tissues and suggest that this macrolide antibiotic represents a valuable option in the pharmacologic treatment of odontogenic infections.
Treatment with piroxicam or azithromycin alone ensures a favorable distribution of these drugs into periodontal tissues. However, upon combined administration, azithromycin interferes negatively with the periodontal disposition of piroxicam. This interaction might depend on the displacement of piroxicam from acceptor sites at the level of periodontal tissues.
The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.
Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed. Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate. While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori strains, respectively. These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H. pylori-associated diseases.
Azithromycin concentrations in the tonsils of 56 pediatric patients, treated with 10 or 20 mg of the drug per kg of body weight for 3 days, were compared. Azithromycin levels in plasma and tonsil samples were determined up to 8.5 days after the last dose. The 20-mg/kg regimen resulted in an improved tonsillar distribution of azithromycin, suggesting the achievement of enhanced therapeutic concentrations at infective sites of the upper respiratory tract.Azithromycin, the prototype of azalides, possesses peculiar pharmacokinetics, consisting of high distribution into target tissues (4), and displays a broad antimicrobial spectrum (12). Guidelines for azithromycin MICs have established that breakpoints of Յ2, 4, and Ն8 mg/liter indicate susceptible, intermediately resistant, and resistant bacteria, respectively (7).Studies with adults have suggested that once-daily dosing with 500 mg for 3 days should maintain tonsillar azithromycin levels higher than 2 mg/kg of body weight for 10 days (3, 4). In pediatric patients, a 3-day treatment with 10 mg/kg allows a tonsillar azithromycin distribution similar to that of adults (15). Cure and improvement rates of 93 to 100% were obtained in children with bacterial pharyngitis and/or tonsillitis treated with 10 mg of azithromycin/kg for 3 days (7). However, lower success rates have also been reported (2, 11).After oral administration, azithromycin undergoes a rapid uptake from systemic circulation into phagocytes, which then release the drug at infection sites, exposing local extracellular compartments to azithromycin concentrations higher than plasma levels (5, 6). On this basis, azithromycin administration at doses higher than standard regimens might improve eradication rates in pharyngitis and tonsillitis. Accordingly, this study compared azithromycin concentrations in tonsils collected from pediatric patients treated with 10 or 20 mg/kg daily for 3 days.The study was performed with children scheduled to undergo surgical tonsil removal. The exclusion criteria were history of drug allergy; drug treatments, including antimicrobials, nonprescription drugs, or enzymatic inducers and/or inhibitors within the previous 2 weeks; conditions affecting drug absorption (vomiting, diarrhea, malabsorption); and major medical problems. Informed consent was obtained from parents or legal guardians. The investigation was approved by the local University Hospital Ethics Committee. Fifty-six patients (30 males, 26 females; age range, 4 to 12 years; mean age, 6.46 Ϯ 0.32 years [mean Ϯ standard deviation]) entered the study. They were assigned to two groups, balanced for sex and age, and were treated once daily with azithromycin in an oral suspension (Zitromax; Pfizer Italiana, Rome, Italy) at 10 or 20 mg/kg for 3 days. Patients underwent surgery from 0.5 to 8.5 days after the last dose. Standard anesthesiological procedures and perioperative medications were applied. All surgical procedures were performed by the same surgeon (P.B.). Plasma samples (2 ml) were collected before surgery. Specimen...
Il crescente impiego di regole di interruzione della terapia basate sulla diminuzione dei livelli virali pre-trattamento, impone l'adozione di test che uniscano alla precisione un ampio range dinamico. Abbiamo valutato le prestazioni del dosaggio Abbott LCx HCV RNA Quantitativo, con range dinamico compreso tra 23 e 2.300.000 UI/mL, basato su estrazione con colonne QIAmp, RT-PCR competitiva e rilevazione automatica MEIA su analizzatore LCx (tempo totale di esecuzione di 24/48 campioni: 6/7 ore). Metodi.Accuratezza, precisione e linearità sono state stabilite con pannello Acrometrix (50, 500, 50.000, 500.000, 1.000.000 UI/mL) mediante 24 repliche per ogni livello (4 x 6 sessioni). La riproducibilità è stata inoltre valutata sui controlli positivi basso ed alto (CP1 e CP2) del kit, analizzati in ogni sessione. 101 campioni di donatori di sangue, negativi per anti-HCV e HCV-RNA, sono stati impiegati per verificare la specificità. Per la correla-zione sono stati analizzati 210 campioni retrospettivi selezionati dalla routine e testati con Cobas Monitor (range dinamico 600 -500.000 UI/mL). Risultati.Il CV totale (log UI/mL) per il pannello era compreso tra 2,7% e 9,2 % e per CP1 e CP2 era di 4,3% e 3,4% rispettivamente. La retta di regressione lineare tra valori LCx (y) e attesi (x) era y = 1,13x -0,48 (R 2 = 0,9966). La frequenza di rilevazione a 50 UI/mL è risultata del 52 % (12/23), mentre il 79% delle repliche a 1.000.000 di UI/mL, era nel range dinamico. La specificità era del 99% (100/101); l'unico campione inizialmente reattivo (26 UI/mL), era negativo alla ripetizione. 37 campioni (17,6% del totale) con risultato Monitor > 500.000 UI/mL, erano nel range dinamico di LCx, mentre solo 6 campioni (2,8%) erano > 2.300.00 con LCx e nel range con Monitor. 9 campioni < 600 UI/mL con Monitor, positivi al test qualitativo, erano dosabili con LCx (range 85-676 UI/mL). Il coefficiente di correlazione r tra LCx e Monitor (74 risultati misurabili per entrambi) era 0,908. Nessun campione ha mostrato differenza superiore a 1 log (media Monitor-LCx = 0,03 log). L'analisi delle differenze ha mostrato una tendenza del metodo LCx a fornire risultati più elevati per valori superiori a 5,5 log (circa 300.000 UI/mL). Conclusioni.Il test Abbott LCx HCV ha mostrato eccellenti precisione e linearità e una buona specificità. Il test ha correlato bene con il dosaggio di confronto, e il più ampio range dinamico si è tradotto -nella casistica analizzata -nel 19% circa in più di risultati refertabili (4% < 600 UI/mL e 15% > 500.000 UI/mL). Sebbene basato su una RT-PCR convenzionale, il test può rappresentare un avanzamento nell'analisi di HCV-RNA, permettendo in teoria di utilizzare un unico dosaggio con duplice scopo qualitativo-quantitativo.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.