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PubMed1996

A comparative study of the efficacy, safety and tolerability of azithromycin and cefaclor in the treatment of children with acute skin and/or soft tissue infections.

An open, multicentre study was carried out in 200 paediatric patients between 6 months and 12 years of age with skin and/or soft tissue infections (mild-to-moderate dermatological conditions and abscesses) to compare the efficacy and safety of azithromycin and cefaclor oral suspensions. Patients were randomly assigned to receive either azithromycin (10 mg/kg once daily for 3 days) or cefaclor (20 mg/kg/day in three divided doses for 10 days). The clinical efficacy of both treatments was comparable: 92/98 (94%) of the evaluable azithromycin patients were cured or improved as were 93/98 (95%) of those treated with cefaclor. Before treatment, 74 pathogens were isolated from 60 of the azithromycin- and 80 pathogens from 66 of the cefaclor-treated patients. In the azithromycin group, 70/74 (95%) pathogens were eradicated, as were 79/80 (99%) pathogens in the cefaclor group. All 200 patients were evaluable for safety analyses. Both drugs were well tolerated, with a low incidence of side-effects: 3/100 (3%) in the azithromycin group and 2/100 (2%) in the cefaclor group. No patient in either treatment group withdrew from the study because of adverse events. In conclusion, azithromycin is as effective and as well tolerated as cefaclor in the treatment of children with skin and/or soft tissue infections.

Acute Disease↗
PubMed1996

An open study to compare azithromycin with cefaclor in the treatment of children with acute otitis media.

An open, multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media. Patients were randomized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days. Cure or improvement in signs and symptoms was observed in 112/114 (98%) evaluable azithromycin-treated patients and 116/120 (97%) evaluable cefaclor-treated patients on days 11-15. In contrast to cefaclor, however, azithromycin was associated with a significantly (P = 0.033) higher cure rate 1 month after completion of treatment. In those patients who were followed up to days 25-30, the response was satisfactory (cure or improvement) in 31/32 (97%) patients who had received azithromycin and in 31/36 (86%) to whom cefaclor had been administered. Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group. The results of this study show that a 3-day, once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days, but the azithromycin is associated with a lower incidence of relapse.

Acute Disease↗
PubMed2000

Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils exposed to azithromycin: effects of Streptococcus pneumoniae.

Pathogen virulence factors and the host inflammatory response cause tissue injury associated with respiratory tract infections. The azalide azithromycin has demonstrated efficacy in the treatment of these infections. It has been demonstrated previously that induction of polymorphonuclear leucocyte (PMN) apoptosis is associated with minimization of tissue damage and inflammation in the lung. We hypothesized that, in addition to its antibacterial effects, azithromycin may promote apoptosis. The aim of the study was to determine the effects of azithromycin on PMN apoptosis, oxidative function and interleukin-8 (IL-8) production in the presence or absence of Streptococcus pneumoniae, in comparison with penicillin, erythromycin, dexamethasone or phosphate-buffered saline. Human circulating PMNs were assessed for apoptosis (by annexin V labelling and ELISA), oxidative function (by nitroblue tetrazolium reduction) and IL-8 production (by ELISA). Azithromycin significantly induced PMN apoptosis in the absence of S. pneumoniae after 1 h (10.27% +/- 1.48%, compared with 2.19% +/- 0.42% in controls) to levels similar to those after 3 h induction with tumour necrosis factor-alpha (8. 73% +/- 1.86%). This effect was abolished in the presence of S. pneumoniae. Apoptosis in PMNs exposed to the other drugs was not significantly different from that in controls. Azithromycin did not affect PMN oxidative metabolism or IL-8 production. In summary, azithromycin-induced PMN apoptosis may be detected in the absence of any effect on PMN function, and the pro-apoptotic properties of azithromycin are inhibited in the presence of S. pneumoniae.

Apoptosis↗
PubMed2001

Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections.

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2002

Comparative pharmacodynamics of azithromycin and roxithromycin with S. pyogenes and S. pneumoniae in a model that simulates in vitro pharmacokinetics in human tonsils.

Most macrolides penetrate and persist in peripheral tissues, irrespective of plasma concentrations. For this reason, comparative pharmacodynamics of macrolides might be better based on tissue rather than plasma pharmacokinetics. The present study compares the antimicrobial effects of azithromycin and roxithromycin on Streptococcus pyogenes and Streptococcus pneumoniae using in vitro simulations of steady-state pharmacokinetics in human tonsils expected after a third 500 mg dose of azithromycin administered once a day and after a sixth 150 mg dose of roxithromycin administered twice a day. Clinical isolates of S. pyogenes and S. pneumoniae (MICs 0.12 and 0.47 mg/L of azithromycin, and 0.15 and 0.60 mg/L of roxithromycin, respectively) were used. More pronounced antistreptococcal effects were observed with azithromycin than with roxithromycin. Despite similar rates of initial killing of S. pyogenes and S. pneumoniae, the respective 12 h areas between the control growth curve and the time-kill curve of antibiotic-exposed bacteria (ABBCs) were 22% and 36% greater with azithromycin than roxithromycin. Moreover, with azithromycin, viable bacterial counts reached the theoretically achievable limit of detection (10 cfu/mL) 8-10 h after drug administration, with no regrowth within 48 h. In contrast to azithromycin, S. pyogenes and S. pneumoniae exposed to roxithromycin regrew 26 and 6 h, respectively, after initial reduction of the starting inoculum. Further in vitro simulations of tissue pharmacokinetics might be useful for pharmacodynamic comparisons among other macrolides.

Anti-Bacterial Agents↗
PubMed2002

In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin.

Pimozide is often coprescribed with serotonin reuptake inhibitor (SSRI) antidepressants to treat depression in patients with Tourette's syndrome. In human liver microsomes (HLMs), the inhibition of the primary route of pimozide metabolism, N-dealkylation to 1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one (DHPBI), by four SSRIs (fluoxetine, sertraline, paroxetine, and fluvoxamine) and azithromycin was tested. Inhibition constants (K(i) values) were estimated from Dixon plots (three HLMs for each inhibitor) using the appropriate enzyme inhibition model by nonlinear regression. At 10 microM paroxetine, sertraline, fluoxetine, or fluvoxamine, the formation of DHPBI from pimozide (10 microM) in HLMs was inhibited by an average (three HLMs) of 7%, 7.7%, 8%, and 16%, respectively, whereas this inhibition did not exceed 55% at the maximum concentrations (100 microM) of the SSRIs tested. Azithromycin had negligible effect on pimozide (10 microM) N-dealkylation (19% at 100 microM azithromycin). These inhibition data were compared with ketoconazole, which was included as a positive control of CYP3A inhibition. At 0.1 microM and 0.5 microM ketoconazole, the formation of DHPBI from 10 microM pimozide was inhibited by 32% and 62%, respectively. The K(i) values (+/- SD) of ketoconazole, sertraline, fluvoxamine, azithromycin, fluoxetine, and paroxetine were 0.07 microM, 89 +/- 44 microM, 89 +/- 24 microM, 103 +/- 52 microM, 117 +/- 27 microM, and 129 +/- 33 microM, respectively. These values are least 100-fold higher than the expected plasma concentrations after the usual daily doses of the SSRIs and azithromycin, suggesting that coadministration of SSRIs and azithromycin are unlikely to markedly diminish the elimination of pimozide in patients. However, in vivo predictions from in vitro data are not always perfect. In vivo, the SSRIs or azithromycin may concentrate in the liver relative to plasma. In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

Properties of azithromycin that enhance the potential for compliance in children with upper respiratory tract infections.

BACKGROUND: Azithromycin, the prototypical azalide antibiotic, has a wide spectrum of activity that is characterized by resistance to beta-lactamase-producing microbes and efficacy against Gram-positive and Gram-negative pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics include tissue concentrations up to 100-fold higher than those in plasma and a tissue half-life of up to 4 days. Pharmacokinetics of azithromycin permits a reduction in dosage frequency and duration while maintaining efficacy comparable to that of conventional 7- to 10-day three or four times daily regimens. Dosage interval, duration of treatment, side effects and palatability can affect compliance and thus clinical outcome. Compliance among children is important in light of the high incidence of community-acquired infections such as otitis media and streptococcal pharyngitis. OBJECTIVE: To compare the flavor, taste acceptability and color preference of oral antibiotic suspensions given to children. METHODS: The taste and acceptability of the oral suspension form of azithromycin vs. cefixime, cefpodoxime proxetil, cefprozil, clarithromycin or loracarbef were rated by children during blinded taste tests and with acceptability/ preference questionnaires. RESULTS: Analysis of the mean acceptability/ preference rating from 769 children demonstrated that the flavor of azithromycin was rated significantly higher than that of cefpodoxime (4.3 vs. 2.8), cefprozil (4.0 vs. 3.4) and clarithromycin (4.3 vs. 2.7) and was comparable to that of cefixime (4.0 vs. 4.2) and loracarbef (4.4 vs. 4.5). A greater percentage of children preferred the taste of azithromycin to that of cefpodoxime (90.0% vs. 5.2%), cefprozil (63.0% vs. 33.1%) and clarithromycin (89.0% vs. 11.0%). The taste of azithromycin was not preferred to that of cefixime (39.0% vs. 53.9%) or loracarbef (36% vs. 58.5%). CONCLUSIONS: The efficacy and safety of azithromycin in otitis media and streptococcal pharyngitis, the simple dosing regimen and a highly palatable oral suspension formulation should increase compliance among pediatric patients and thereby improve clinical outcomes.

Administration, Oral↗
PubMed1998

Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.

OBJECTIVE: To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. METHODS: Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy. RESULTS: Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05). CONCLUSION: Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.

Adolescent↗
PubMed1999

Impact of community-based mass treatment for trachoma with oral azithromycin on general morbidity in Gambian children.

BACKGROUND: The World Health Organization has recently targeted the elimination of trachoma as a public health problem by the year 2020. Community-based treatment with antibiotics, including oral azithromycin, is recommended for severely affected communities. The incidence of adverse effects after azithromycin treatment is not known in trachoma endemic communities. METHODS: We compared the effects of azithromycin with those of topical tetracycline given as mass treatment for trachoma on childhood morbidity in eight rural Gambian villages. The entire population of four villages received oral azithromycin suspension (Zithromax, Pfizer) in doses of 20 mg/kg on Days 1, 8 and 15; the other four villages received topical tetracycline eye ointment for 42 days. Morbidity surveys of subjects 3 months to 14 years old were conducted on Days 0, 7, 14, 21 and 28. RESULTS: Of the 804 subjects recruited complete follow-up data were available on 791 (412 azithromycin, 379 tetracycline). Fever and headache were the most common complaints. Apart from cough other symptoms were equally prevalent in both groups at baseline. The azithromycin group had 20% fewer illness, fever and headache episodes and 40% fewer diarrhea and vomiting episodes at follow-up than did the tetracycline group. CONCLUSIONS: Azithromycin treatment for trachoma had favorable short term effects on childhood morbidity in rural Gambian villages, particularly in the high malaria transmission season, and adverse effects were not a problem.

Administration, Oral↗
PubMed2002

A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.

BACKGROUND: Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients. Preliminary data suggest that azithromycin may be effective for syphilis therapy. STUDY DESIGN: This was a randomized, comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis. METHODS: We randomly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally, either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart. Serological response to therapy was evaluated at 3, 6, 9, and 12 months following therapy. Participants whose rapid plasma reagin (RPR) test became nonreactive or whose RPR titer decreased > or =2 dilutions were classified as responding to therapy. When serological tests did not show a response to therapy, the treatment was classified as a failure if RPR titers increased > or =2 dilutions. Nonresponders were those whose serologic titers remained within +/-1 dilution of the initial RPR titer. RESULTS: Cumulative response rates were as follows: benzathine penicillin G, 86% (12 of 14); azithromycin, 2.0-g single dose, 94% (16 of 17); and azithromycin, two 2.0-g doses given 1 week apart, 83% (24 of 29). Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen, whereas in six patients the clinical manifestations of infection resolved but there was no serological response. CONCLUSION: Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further.

Administration, Oral↗
PubMed2004

Single dose azithromycin for the treatment of uncomplicated otitis media.

Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM). In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone. A second, non-comparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen. The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate. The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM. In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001). We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children.

Azithromycin↗
PubMed2005

Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda.

OBJECTIVE: The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis. METHODS: In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression. RESULTS: Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80-0.99) and in subjects with initial titers > or =1:4 compared with < or =1:2 (RR, 0.77; 95% CI, 0.69-0.86). There was no significant differences in cure rates among HIV-positive and HIV-negative persons. With initial titers < or =1:2, there were no differences in cure rates by treatment regimen. However, with initial titers > or =1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97-1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03-1.87) compared with penicillin alone. CONCLUSION: Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates.

Adolescent↗
PubMed1995

Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats.

Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL. The harmonic mean terminal t1/2 after i.v. administration was 35 h. Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin.

Absorption↗
PubMed1991

Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450.

Erythromycin and some other macrolide antibiotics can first induce a cytochrome P-450 isozyme similar to the one induced in rats by pregnenolone-16 alpha-carbonitrile and then inhibit it by forming a stable cytochrome P-450-metabolite complex. The purpose of this study was to compare azithromycin, a novel 15-membered ring azalide, and erythromycin estolate for the potential to cause hepatic microsomal enzyme induction and inhibition in Sprague-Dawley rats. The daily oral administration of 800 mg of erythromycin estolate per kg for 7 days resulted in statistically significant elevations of NADPH-cytochrome c reductase, erythromycin N-demethylase (3.2-fold), and total cytochrome P-450 content. Approximately 40% of cytochrome P-450 was complexed with erythromycin metabolite. In contrast, the daily administration of 200 mg of azithromycin per kg for 7 days caused significant elevations of N-demethylase (2.5-fold) only and did not produce any increases in total cytochrome P-450 content or NADPH-cytochrome c reductase. No complexed cytochrome P-450 was detected in the azithromycin-dosed rats despite liver concentrations of azithromycin that were 118 times greater than the liver concentrations of erythromycin estolate in erythromycin estolate-dosed rats. Although the short-term oral administration of azithromycin produced hepatic accumulation of the drug and elevated azithromycin demethylase activity, there was no other evidence of hepatic cytochrome P-450 induction or inactivation via cytochrome-metabolite complex formation. In contrast to erythromycin estolate, azithromycin is not expected to inhibit its own metabolism or that of other drugs via this pathway.

Animals↗
PubMed1992

Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin.

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Animals↗
PubMed1992

Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection.

We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods. The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells. This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time.

Administration, Oral↗
PubMed1993

Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension.

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.

Administration, Oral↗
PubMed1994

Intracellular activity of azithromycin against bacterial enteric pathogens.

Azithromycin, a new azalide antibiotic, is active in vitro against a variety of enteric bacterial pathogens. Since it is concentrated inside human neutrophils and other cells, it might be particularly useful in the treatment of infections caused by enteropathogens that invade host tissues. The intracellular activity of azithromycin against several enteric pathogens that had been phagocytosed by neutrophils was determined. Azithromycin was effective in reducing the intracellular viabilities of almost all strains tested, including representative strains of Salmonella, Shigella, and enteroinvasive, enteropathogenic, enterotoxigenic, and enterohemorrhagic Escherichia coli. Erythromycin was also effective in this model system, although azithromycin was generally more effective than erythromycin against strains of invasive enteric pathogens. Cefotaxime reduced intracellular bacterial viability to a lesser extent than either azithromycin or erythromycin. The presence of neutrophils did not significantly affect the activity of azithromycin in this system. Azithromycin may be a useful agent for the treatment of bacterial diarrhea, and clinical trials should be considered.

Azithromycin↗