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PubMedDate not supplied

Azithromycin compared with clarithromycin for the treatment of streptococcal pharyngitis in children.

The treatment of streptococcal pharyngitis with azithromycin (10 mg/kg orally once daily for 3 days) or clarithromycin (7.5 mg/kg orally twice daily for 10 days) was compared in a randomized observer-blind study carried out in 174 children with documented Streptococcus pyogenes infection. The observed cure rate 10 days after the beginning of treatment was 61/63 (96.8%) in the clarithromycin group and 71/74 (95.9%) in the azithromycin group. At days 17-20 the bacteriological eradication rate was 95.2% for clarithromycin and 94.6% for azithromycin. When children who did not complete treatment were included in the analysis the eradication rate was higher for azithromycin (93.6% compared with 82.9%; P < 0.05); the difference was due to better compliance with the azithromycin regimen.

Adolescent↗
PubMedDate not supplied

Azithromycin vs doxycycline in the treatment of non-gonococcal urethritis.

Azithromycin is a novel azalide macrolide active against Chlamydia trachomatis and Ureaplasma urealyticum. High persistent tissue concentrations allow short courses or even single doses to be considered. Sixty-two patients were studied, 19 received azithromycin 1 g in a single dose, 22 received azithromycin 500 mg in a single dose on day 1 followed by 250 mg once daily for 2 days and 21 received doxycycline 200 mg in a loading dose followed by 100 mg every 12 h for 7 days. Efficacy of these 3 regimens was compared in the treatment of non-gonococcal urethritis (NGU). Clearance of C. trachomatis from post-treatment cultures was satisfactory with all regimens. Response defined as the absence of symptoms and reduction in polymorphonuclear leucocytes in a Gram stained smear of urethral secretion to less than 5 cells per hpf (x 100 objective) was statistically better for the 3 day regimen of azithromycin than for the other 2 regimens. All treatments were well tolerated. Three days or single doses of azithromycin compared to 7 days of tetracycline (or 10-14 days as is often prescribed) have obvious advantages for patient compliance.

Administration, Oral↗
PubMed1995

Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis.

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1997

Comparative trial of azithromycin and ciprofloxacin in the treatment of gonorrhea.

This single-blind (investigator) comparative study was designed to determine the efficacy and tolerability of 1 g of azithromycin vs 500 mg of ciprofloxacin both given as a single oral dose in patients with gonorrhea, who were constantly on the move. One hundred eight patients (59 men and 49 women) with clinically suspected gonococcal infection, confirmed by Gram-stain and culture, were enrolled. Data of 50 patients treated with azithromycin and 51 with ciprofloxacin were evaluable for efficacy and tolerability at the end of the study. After 2 weeks clinical and microbiological cure rates were 96.0% (48 out of 50) for the patients treated with azithromycin and 92.15% (47 out of 51) for the patients treated with ciprofloxacin (p > 0.05). Adverse reactions were reported in 5 patients treated with azithromycin and 6 with ciprofloxacin. In conclusion, 1 g azithromycin is at least as clinically and microbiologically effective and well tolerated as 500 mg of ciprofloxacin in the treatment of gonococcal infections. The drug is particularly useful for sailors and people constantly on the move.

Administration, Oral↗
PubMed1998

Azithromycin compared with minocycline in the treatment of acne comedonica and papulo-pustulosa.

This open study was conducted in 72 outpatients with acne vulgaris, to compare the clinical efficacy and tolerability of azithromycin and minocycline. Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles every 10 days and minocycline was administered 100 mg daily for 6 weeks. Improvement was assessed 6 weeks after initiation of treatment with a four-graded scale. A satisfactory clinical response was observed in 75.8% of the patients treated with azithromycin and in 70.5% of those treated with minocycline. There were no significant differences between these two acne treatments in terms of reduction of the number of lesions (p> 0.05). Both agents were well tolerated and mild side effects were reported in 10.3% of azithromycin and 11.7% of minocycline treated patients. We conclude that azithromycin is at least as clinically effective and well tolerated as minocycline as treatment of facial comedonic and papulopustular acne.

Acne Vulgaris↗
PubMed2006

In vitro induction of resistance by tissue concentrations of azithromycin, clarithromycin, cefixime and amoxicillin/clavulanate in clinical isolates of Streptococcus pyogenes.

This study evaluated the effects of exposure to serum, tonsils and breakpoint drug concentrations of clarithromycin, azithromycin, cefixime and amoxicillin/clavulanate on Streptococcus pyogenes susceptibility. Frequency of mutation and development of resistance after ten passages on antibiotic gradient plates, followed by ten passages without antibiotic, were determined. Phenotypes of macrolide-resistant strains grown at the end of multi-step selection were also determined. Azithromycin induced a surge of resistant strains more rapidly and frequently than clarithromycin, particularly at tonsils concentrations. With amoxicillin/clavulanate no strains showed minimum inhibitory concentrations (MICs) higher than the susceptibility breakpoint. Mutational frequencies were higher for azithromycin, at serum and breakpoint drug concentrations, than for the other drugs. Most of the macrolide resistant strains showed an MLS(B) phenotype. In conclusion, the ability to prevent the occurrence of resistance in clinical isolates of S. pyogenes was similar for amoxicillin/clavulanate and clarithromycin followed by cefixime > azithromycin when tonsil drug concentrations were considered, and greater for amoxicillin/clavulanate followed by clarithromycin > cefixime> azithromycin, at breakpoint and serum concentrations.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2001

[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent].

Azithromycin (Zithromac), a 15-membered ring macrolide antibacterial agent, was approved to be manufactured in Japan in March 2000. It showed good in vitro and/or in vivo antibacterial activities against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Peptostreptococcus micros, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae. Its activity against H. influenzae was particularly more potent than that of currently used macrolide antibacterial agents. After oral administration to patients, azithromycin was readily absorbed and became widely distributed throughout the body, achieving higher concentrations in tissues and phagocytic cells than in serum or plasma. Its distribution into phagocytes was as high as more than 10 times that of erythromycin, and azithromycin was readily released from phagocytes in the presence of S. aureus. In experimentally infected mice, the concentration of azithromycin was higher in infected tissues than in uninfected tissues, which indicated that azithromycin was selectively delivered to infected tissues by migrating phagocytes. These pharmacological and pharmacokinetic properties were reflected in good clinical results for the treatment of respiratory infections and other infections with once daily dosing for 3 days.

Adult↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of intravenous and oral azithromycin: enhanced tissue activity and minimal drug interactions.

OBJECTIVE: To review the pharmacokinetics and pharmacodynamics of oral and intravenous azithromycin compared with other macrolide antibiotics, and to evaluate these differences and their relation to clinical effectiveness. DATA SOURCE: A MEDLINE search (1966-May 1998) was performed to identify applicable English-language clinical, animal, and microbiologic studies pertaining to pharmacokinetic and pharmacodynamic parameters. STUDY SELECTION: Relevant studies concerning microbiology, pharmacokinetics, tissue concentrations, pharmacodynamics, and the clinical effects of these parameters were selected. DATA SYNTHESIS: The structural modification that distinguishes the azalide antibiotics from the macrolide antibiotics is responsible for the pharmacokinetic and pharmacodynamic behavior of azithromycin, resulting in the high and sustained tissue and intracellular concentrations seen with this agent. Drug delivery to the site of infection by phagocytes and fibroblasts is the hallmark of azithromycin's tissue-directed pharmacodynamics, allowing for convenient once-daily, 5-day regimens for most infections that respond to oral therapy and 7-10 days for more serious infections requiring initial intravenous therapy. Metabolism is via hepatic pathways other than cytochrome P450, thus minimizing the risk of drug interactions. CONCLUSIONS: Compared with other macrolide antibiotics, the unique pharmacokinetic and pharmacodynamic features of azithromycin offer the potential for improved efficacy and safety from drug interactions. These attributes, combined with its once-daily dosing schedule, make azithromycin suitable for the treatment of many types of bacterial infection.

Administration, Oral↗
PubMed1999

Intravenous azithromycin.

OBJECTIVE: To review the pharmacology, microbiology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous azithromycin. DATA SOURCES: A MEDLINE search from 1978 to May 1998 of the English-language literature and an extensive review of journals and meeting abstracts was conducted. Due to the lack of published literature concerning the efficacy, safety, and pharmacokinetics of the intravenous formulation of azithromycin, the manufacturer was also contacted and requested to supply information concerning intravenous azithromycin. DATA EXTRACTION: In vitro and preclinical studies were included, as well as data from Phase II and III clinical trials. Efficacy, pharmacokinetic, safety, and tolerability data were also supplemented with information from the manufacturer, due to the lack of published reports. DATA SYNTHESIS: Azithromycin, an azalide subclass of the macrolide antibiotics, is now available as an intravenous formulation. The intravenous form is approved for the treatment of community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae. Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus (methicillin-sensitive), and Streptococcus pneumoniae, and for the treatment of pelvic inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in situations in which intravenous therapy is required. Its spectrum of activity, unique pharmacokinetics, and high and sustained tissue penetration allow for once-daily dosing with monotherapy in many cases. Clinical and bacteriologic response rates as well as the adverse event profile have been similar to or better than comparative agents. CONCLUSIONS: Azithromycin offers advantages over other agents due to its unique pharmacokinetics, high and sustained tissue penetration, and spectrum of activity. This allows for monotherapy and once-daily intravenous dosing for mild-to-moderate community-acquired pneumonia or pelvic inflammatory disease in many instances. Future research should focus on total duration of antibiotic therapy and the need, or lack thereof, for extensive oral antibiotic follow-up.

Anti-Bacterial Agents↗
PubMed1999

A time-kill evaluation of clarithromycin and azithromycin against two extracellular pathogens and the development of resistance.

OBJECTIVE: To determine the activity of clarithromycin, its metabolite (14-hydroxyclarithromycin), and azithromycin against Haemophilus influenzae and Staphylococcus aureus using time-kill methodology and to evaluate the susceptibility of the organisms following exposure to various concentrations of the azalide macrolides. DATA SOURCES AND METHODS: Clinical isolates of H. influenzae and S. aureus were obtained from the Clinical Microbiology Laboratory at University Hospital, San Antonio, Texas. Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards guidelines. 14-Hydroxyclarithromycin was added to clarithromycin solutions used for H. influenzae. Time-kill studies were performed using antimicrobial concentrations of 0.25-8x minimum inhibitory concentration (MIC) and an initial inoculum of approximately 10(5) CFU/mL. Samples were plated onto solid agar at 0, 4, 8, 12, and 24 hours. At 0, 12, and 24 hours, samples were then plated onto solid agar incorporated with antibiotic. After incubating plates at 35 degrees C for 24 hours, colony counts were determined. RESULTS: The MICs of clarithromycin and clarithromycin plus 14-hydroxyclarithromycin for H. influenzae were 4 and 2 microg/mL, respectively. For S. aureus, the MIC of clarithromycin was 0.25 microg/mL, and the MIC of azithromycin for both organisms was 1 microg/mL. H. influenzae developed resistance to both macrolides within 12 hours when exposed to sub-MICs of clarithromycin plus 14-hydroxyclarithromycin. However, when exposed to concentrations less than or equal to the MIC of azithromycin, resistance was not conferred to clarithromycin. S. aureus, on the other hand, became resistant to azithromycin and less susceptible to clarithromycin following exposure to sub-MICs of either macrolide. CONCLUSIONS: Clarithromycin and azithromycin elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.

Anti-Bacterial Agents↗
PubMed2003

Efficacy and safety of azithromycin vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis.

STUDY OBJECTIVES: To compare the safety and efficacy of oral azithromycin and levofloxacin in the treatment of outpatients with acute bacterial exacerbations of chronic bronchitis (ABECB). DESIGN: Randomized, double-blinded, double-dummy, multicenter trial with 1:1 treatment allocation. SETTING: Outpatient treatment setting. PATIENTS: Two hundred thirty-five male or female outpatients between the ages of 35 and 75 years who had received a clinical diagnosis of ABECB. INTERVENTIONS: Blinded treatment with either oral azithromycin, 500 mg on day 1 and 250 mg per day for days 2 to 5, or, oral levofloxacin, 500 mg q24h for 7 days. RESULTS: Both treatments were well-tolerated, with the majority of adverse events being GI in nature. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24, the posttherapy visit, favorable responses were approximately 82% and 86%, respectively, for patients in the two treatment groups. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin. CONCLUSIONS: Despite increasing concerns over macrolide resistance and a higher incidence of Gram-negative pathogens, a standard 5-day course of oral azithromycin was clinically and bacteriologically equivalent to a 7-day course of oral levofloxacin in the treatment of patients with ABECB.

Acute Disease↗
PubMed2006

Azithromycin does not cure pityriasis rosea.

OBJECTIVES: Pityriasis rosea (PR) is a common skin disorder in children. Its cause is unknown. A recent publication reported a 73% cure rate in patients with PR after treatment with erythromycin. To duplicate this result using a drug with fewer adverse effects and greater biological half-life, we set out to study the effect of azithromycin on PR. Azithromycin is an azalide antibiotic with a spectrum of antimicrobial activity very similar to that of erythromycin. DESIGN: We randomly assigned 49 children with PR to receive either azithromycin (12 mg/kg per day, up to a maximum of 500 mg/day) for 5 days or a similar-appearing placebo. Study physicians were blinded to patients' treatment type. Two pediatricians had to agree on the diagnosis of PR before patients could be enrolled. Subjects were seen at follow-up visits 1, 2, and 4 weeks after starting treatment. OUTCOME MEASURES: We measured the appearance of new lesions and resolution of lesions. RESULTS: Rates of cure and of partial resolution were similar in the azithromycin and placebo groups. CONCLUSION: Azithromycin does not cure PR.

Anti-Bacterial Agents↗
PubMed2001

Possible interaction between intravenous azithromycin and oral cyclosporine.

A 42-year-old man who had received a cadaveric kidney transplant 9 years earlier was admitted to the hospital with pneumonia. His oral cyclosporine dosage for the past 2 years was stabilized at 100 mg twice/day; his cyclosporine whole blood trough levels 15 days earlier and on the day he was admitted were both 178 ng/ml. The patient was treated with intravenous ceftriaxone and intravenous azithromycin and continued to receive the same dosage of oral cyclosporine. On hospital day 3, his cyclosporine trough level rose to 400 ng/ml and his dosage was reduced by 50%. Trough levels were 181 ng/ml and 175 ng/ml on hospital days 6 and 9, respectively On hospital day 9, the patient stopped receiving azithromycin. On hospital day 14, his cyclosporine trough level dropped to 76 ng/ml, and his cyclosporine dosage was increased back to 100 mg twice/day. The dosage produced trough levels consistent with those before he had been admitted. The patient was discharged on day 20, and a follow-up cyclosporine trough level determined 3 weeks later was 175 ng/ml. Administration of azithromycin may have caused the increased cyclosporine concentrations in this patient through p-glycoprotein inhibition and/or competition for biliary excretion. Azithromycin's interference may be inferred by the increase in cyclosporine levels after administration of this drug and the decrease in cyclosporine levels after its discontinuation-both consistent with the pharmacokinetic properties of cyclosporine. Ceftriaxone and acute-phase reactant activation during infection, however, also may have interfered with the patient's cyclosporine elimination. Azithromycin generally is considered unlikely to interact with cyclosporine. Nonetheless, practitioners should be aware of this possibility and should monitor cyclosporine levels closely, especially in critically ill patients who have other complications.

Administration, Oral↗
PubMed1993

Azithromycin clinical pharmacokinetics.

Azalide antibiotics, of which azithromycin is the first demonstrated, have different pharmacokinetics from other antibiotics currently used. The bioavailability of the drug is approximately 37%. Extensive and rapid distribution from serum into the intracellular compartments is followed by rapid distribution to the tissues. Tissue concentrations exceed serum concentrations by up to 100-fold following a single azithromycin 500mg dose. Concentration of the drug within phagocytes aids in its ability to combat infections. High concentrations of azithromycin are found in the tonsil, lung, prostate, lymph nodes and liver, with only small concentrations found in fat and muscle. A 500mg dose on day 1, followed by 250mg daily on days 2 to 5, has been demonstrated to maintain azithromycin concentrations at sites of infection and continues to be effective for several days after administration has ceased. The pharmacokinetics of azithromycin make it a drug with diverse therapeutic applications.

Azithromycin↗
PubMed2001

Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.

OBJECTIVE: To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. ANIMALS: 6 healthy 6- to 10-week-old foals. PROCEDURE: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. RESULTS: Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min x kg, and apparent volume of distribution at steady state was 18.6 L/kg. After i.g. administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated i.g. administration, peak serum concentration was 0.63 +/- 0.10 microg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated i.g. administration. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.

Administration, Oral↗
PubMed2001

Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin.

OBJECTIVES: To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin. ANIMALS: 18 young adult domestic shorthair cats of both sexes. PROCEDURES: Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis. Beginning 26 days after inoculation, 11 cats were administered azithromycin (15 mg/kg of body weight, PO, q 12 h, for 7 days). RESULTS: Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR. Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats. Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation. Administration of azithromycin had little effect on clinical variables, including anemia. All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected. Results of the PCR were superior to results of CBC for detecting infection with H felis. Azithromycin administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis.

Anaplasmataceae↗
PubMed1996

Efficacy and safety of azithromycin versus lymecyline in the treatment of genital chlamydial infections in women.

To compare the clinical and microbiological efficacy of azithromycin in curing chlamydial infections in women with that of lymecycline, and with a view of the possibility of minimizing the problem of compliance by means of single-dose administration, 146 women with culture-positive Chlamydia trachomatis infections were randomly assigned to treatment with a 1 g bolus dose of azithromycin or a 10-day course of lymecycline 300 mg twice daily. Clinical and microbiological evaluations were performed and adverse effects monitored at check-ups after 15-35 and 40-65 days. Of the 146 patients enrolled in the study, 120 were evaluable. At the second check-up, C. trachomatis was found to have been eradicated in all patients in both treatment groups. Of the 51 patients who had clinical signs and symptoms of genital infection at enrolment, 96% (22/23) of those in the azithromycin group were considered cured (n = 18) or improved (n = 4), as compared with 100% (28/28) of those considered cured (n = 22) or improved (n = 6) in the lymecycline group. Adverse events related, or possibly related, to treatment were reported by 16 (21.6%) of the lymecycline group, but by only 6 (8.3%) of the azithromycin group. The 2 drugs were comparable with regard to microbiological and clinical efficacy in the treatment of genital chlamydial infection in women. The markedly lower rate of side-effects associated with azithromycin may be a feature conducive to patient compliance.

Adult↗
PubMed1995

In vivo evaluation of three acid-stable azalide compounds, L-701,677, L-708,299 and L-708,365 compared to erythromycin, azithromycin and clarithromycin.

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Animals↗