zithromax and Gram-Positive-Bacterial-Infections

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

Topics: Azithromycin; Drug Interactions; Erythromycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious

The acronym SAPHO was introduced in 1987 to unify the various descriptions of a seronegative arthritis associated with skin manifestations and to show synovitis, acne, pustulosis, hyperostosis, and osteitis with and without sterile multifocal osteomyelitis. The etiology of SAPHO syndrome is unknown, but an association with infection by semipathogenic bacteria like Propionibacterium acnes has been suggested. We conducted an interventional study of SAPHO patients receiving antibiotics.. Thirty-seven patients met the clinical criteria of SAPHO syndrome, 21 of them underwent a needle biopsy of the osteitis lesion, and 14 of them showed positive bacteriological cultures for P. acnes. Thirty patients (14 bacteriological positive and 16 without biopsy) were treated with antibiotics for 16 weeks. The activity of skin disease and osteitis were assessed by a physician using a scoring model (from 0 to 6). In addition, patients completed a Health Assessment Score (HAS, from 0 to 6). The erythrocyte sedimentation rate was determined and a MRI (of the osteitis lesion, radiologic activity score from 0 to 2) was performed in week 1 (W1), week 16 (W16), and week 28 (W28, 12 weeks after antibiotics).. Twenty-seven patients continued the medication (azithromycin, n = 25, 500 mg twice a week; clindamycin, n = 1, 300 mg daily; or doxycycline, n = 1, 100 mg daily) for 16 weeks. After W16 the scores for MRI (1.5 to 1.1, P = 0.01), skin activity (3.2 to 1.2, P = 0.01), osteitis activity (4.0 to 2.1, P = 0.02), and HAS (3.3 to 2.1, P = 0.01) decreased significantly. However, this was followed by increasing values for MRI scores (1.2 to 1.4, P = 0.08), skin activity (1.2 to 1.7, P = 0.11), osteitis activity (1.9 to 2.7, P = 0.01), and HAS (2.2 to 3.3, P = 0.02) from W16 to W28. The comparison of the scores in W1 and W28 in these 12 patients showed no significant differences.. For the period of application, the antibiotic therapy seems to have controlled the disease. After antibiotic discontinuation, however, disease relapse was observed. SAPHO syndrome thus groups with other chronic inflammatory arthropathies with a need for permanent therapy.

Topics: Acquired Hyperostosis Syndrome; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Clindamycin; Doxycycline; Female; Gram-Positive Bacterial Infections; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Propionibacterium acnes; Treatment Outcome; Young Adult

To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis.. Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study.. Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy.. Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups.. Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Conjunctivitis, Bacterial; Double-Blind Method; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Ophthalmic Solutions; Pharmaceutical Vehicles; Prospective Studies

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacteremia; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Gardnerella vaginalis; Gram-Positive Bacterial Infections; Humans; Immunocompetence; Male; Metronidazole; Recurrence; Sex Distribution; Urethritis

Although polymicrobial infections, such as peri-implantitis or periodontitis, were postulated in the literature to be caused by synergistic effects of bacteria, these effects remain unclear looking at antibiotic susceptibility. The aim of this study is to compare the antibiotic susceptibilities of pure cultures and definite cocultures.. Laboratory strains of Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), Capnocytophaga ochracea (Co), and Parvimonas micra (Pm) (previously Peptostreptococcus micros) were cultivated under anaerobic conditions, and their susceptibilities to 10 antibiotics (benzylpenicillin G, ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, minocycline, metronidazole, linezolid, azithromycin, and moxifloxacin) were tested using the Epsilometertest. Cocultures, each consisting of two or three bacteria, were treated analogously.. All four cocultures showed lower susceptibilities to azithromycin and minocycline than to pure cultures. The coculture Aa-Co showed a lower susceptibility to moxifloxacin as did the coculture Aa-Pm to benzylpenicillin G; the coculture Co-Pm showed a lower susceptibility to amoxicillin, amoxicillin/clavulanic acid, metronidazole, and benzylpenicillin G. However, the coculture Co-Pm showed a higher susceptibility to ampicillin, linezolid and moxifloxacin as did Aa-Pm and Aa-Co-Pm to linezolid.. In addition to established in vitro assays, it was demonstrated that antimicrobial cocultures caused antibiotic susceptibilities that differed from those of pure cultures. Bacterial cocultures frequently showed lowered susceptibilities to antibiotics.

Topics: Acetamides; Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Capnocytophaga; Coculture Techniques; Coinfection; Drug Resistance, Bacterial; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Linezolid; Metronidazole; Microbial Interactions; Minocycline; Moxifloxacin; Oxazolidinones; Penicillin G; Peptostreptococcus; Peri-Implantitis; Periodontitis; Quinolines; Sulbactam

Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed in inflammatory lesions caused by infectious agents such as bacteria and fungi but not in normal tissues or non-infectious lesions. There is evidence that macrolide antibiotics can act as immunomodulatory agents. The purpose of the current study was to determine whether azithromycin, a type of macrolide antibiotic, could reduce the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis in vitro and in vivo. We treated THP-1 cells with LPS, LPS+TREM-1/Fc, and LPS+azithromycin for in vitro study. A B. pyocyaneus pyemia animal model was developed for in vivo study. RT-PCR, western blotting, and flow cytometry (FCM) were employed to determine the expression of TREM-1. ELISA analysis was utilized to examine the concentration of cytokines. Our results showed that azithromycin treatment did not reduce the level of LPS-induced TREM-1 mRNA in THP-1 cells. However, treatment with TREM-1/Fc fusion protein or azithromycin reduced the effect of LPS-stimulated TREM-1 protein expression. The expression of inflammatory factors (TNF-α, IL-6, and IL-1β) in cell culture supernatant and mouse serum of the TREM-1/Fc fusion protein-treated and azithromycin-treated groups were lower than that of the control group (p<0.05). The results from the animal sepsis model experiments demonstrated that the TREM-1 Fc/fusion protein and azithromycin treatment groups' survival rates were significantly higher than in the control group. Analysis of serum inflammatory factors in septic mice revealed that the concentration of these factors was significantly lower than in the control group. Our results furthered the understanding of azithromycin function in immunological regulation and provided reliable data for new clinical applications.

Topics: Animals; Azithromycin; Bacillus; Blotting, Western; Cell Line; Disease Models, Animal; Gene Expression; Gram-Positive Bacterial Infections; Immunoconjugates; Immunomodulation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Receptors, Immunologic; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sepsis; Survival Rate; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10x MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Quinolones; Thiazoles

Peptostreptococcus anaerobius sensu lato, currently including two closely related species, P. anaerobius and P. stomatis, is known to be more resistant than other gram-positive anaerobic cocci. We reidentified potential Peptostreptococcus isolates and tested their susceptibilities to eight antimicrobials. Notably, P. anaerobius had constantly higher values for the MIC at which 50% of the isolates are inhibited (MIC(50)) and the MIC(90) than P. stomatis.

Topics: Anaerobiosis; Anti-Bacterial Agents; Bacteremia; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Peptostreptococcus; Species Specificity

As a result of the prolonged half-life and unique pharmacokinetic and pharmacodynamic (PK-PD) characteristics of azithromycin, shorter dosing regimens are being evaluated for the treatment of community-acquired infections. To provide further support for a shorter dosing regimen, the efficacy of azithromycin was determined in preclinical infection models comparing single- versus multi-dose regimens.. The efficacy of single versus multi-dose regimens of azithromycin was compared in mouse pneumonia, acute peritonitis, and neutropenic thigh infection models and in a gerbil model of Haemophilus influenzae acute otitis media. Azithromycin was administered as a single oral dose on the first treatment day, or as two divided doses over 2 treatment days, or as three divided doses over 3 treatment days. The pharmacokinetics of azithromycin was profiled following single and multi-dose regimens with the single dose data fit to an Emax model to characterize the PK-PD of azithromycin.. In the mouse efficacy models, administration of single-dose azithromycin produced superior rates of survival and bacterial clearance compared with the same total dose divided over 2 or 3 days. In the gerbil model, a single dose sterilized the middle ear and more rapidly cleared H. influenzae. The pharmacokinetic evaluation confirmed similar total exposure (AUC) in serum and pulmonary tissue for the three regimens. Correlation of PK-PD parameters and antimicrobial efficacy confirmed a concentration-dependent and dosing-independent relationship for azithromycin.. These data are consistent with data reported from clinical studies and indicate that a single-dose regimen would be at least as effective as the same dose administered over several days.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Enterococcus faecalis; Female; Gerbillinae; Gram-Positive Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Metabolic Clearance Rate; Mice; Mice, Inbred DBA; Streptococcus pneumoniae; Streptococcus pyogenes