zithromax and Gram-Negative-Bacterial-Infections

Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.

Topics: Azithromycin; Bronchiolitis Obliterans; Gastroesophageal Reflux; Gram-Negative Bacterial Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Diseases; Lung Transplantation; Pneumonia; Pneumonia, Aspiration; Transplantation, Homologous

Azithromycin is a new macrolide antibiotic developed by Pfizer. This compound has a 15 ring structure formed by adding a methyl-nitrogen to the 14-member lactone ring of erythromycin. Azithromycin has acid stability and significant improved activity against gram negative bacteria compared to other macrolides. Further, sustained high tissue levels of azithromycin have been demonstrated clinically and in basic research. There has been particular interest in the phagocyte delivery system of azithromycin to the site of infection. The mechanism is characterized by the intake of azithromycin by phagocytic cells which release the antibiotic at the site of infection. This report describes the mechanism of sustained high tissue levels by summarizing the data of Japanese and western clinical trials and research.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Biological Transport; Disease Models, Animal; Gram-Negative Bacterial Infections; Humans; Mice; Phagocytes; Rats; Tissue Distribution

Azithromycin possesses in position 9 of the lactone cycle a nitrogen atom which provides a second site of protonation. Hence, and compared to erythromycin, azithromycin is more stable in the gastric environment, enjoys improved digestive absorption and improved digestive toleration, displays much higher intracellular accumulation responsible for prolonged serum and tissue half-lives, which allows simplified therapeutic schedules. It is also postulated that improved activity against Gram negative isolates such as H. influenzae and B. catarrhalis results from the same structural particularities.

Topics: Anti-Bacterial Agents; Azithromycin; Erythromycin; Female; Gram-Negative Bacterial Infections; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Palatine Tonsil; Phagocytosis; Prostate; Uterus

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

Azithromycin and clarithromycin are erythromycin analogues that have recently been approved by the FDA. These drugs inhibit protein synthesis in susceptible organisms by binding to the 50S ribosomal subunit. Alteration in this binding site confers simultaneous resistance to all macrolide antibiotics. Clarithromycin is several-fold more active in vitro than erythromycin against gram-positive organisms, while azithromycin is 2- to 4-fold less potent. Azithromycin has excellent in vitro activity against H influenzae (MIC90 0.5 microgram/ml), whereas clarithromycin, although less active against H influenzae (MIC90 4.0 micrograms/ml) by standard in vitro testing, is metabolized into an active compound with twice the in vitro activity of the parent drug. Both azithromycin and clarithromycin are equivalent to standard oral therapies against respiratory tract and soft tissue infections caused by susceptible organisms, including S aureus, S pneumoniae, S pyogenes, H influenzae, and M catarrhalis. Clarithromycin is more active in vitro against the atypical respiratory pathogens (e.g., Legionella), although insufficient in vivo data are available to demonstrate a clinical difference between azithromycin and clarithromycin. Superior pharmacodynamic properties separate the new macrolides from the prototype, erythromycin. Azithromycin has a large volume of distribution, and, although serum concentrations remain low, it concentrates readily within tissues, demonstrating a tissue half-life of approximately three days. These properties allow novel dosing schemes for azithromycin, because a five-day course will provide therapeutic tissue concentrations for at least ten days. Clarithromycin has a longer serum half-life and better tissue penetration than erythromycin, allowing twice-a-day dosing for most common infections. Azithromycin pharmacokinetics permit a five-day, single daily dose regimen for respiratory tract and soft tissue infections, and a single 1 g dose of azithromycin effectively treats C trachomatis genital infections; these more convenient dosing schedules improve patient compliance. Azithromycin and clarithromycin also are active against some unexpected pathogens (e.g., B burgdorferi, T gondii, M avium complex, and M leprae). Clarithromycin, thus far, appears the most active against atypical mycobacteria, giving new hope to what has become a difficult group of infections to treat. Gastrointestinal distress, a well known and major obstacle to patient complia

Topics: Azithromycin; Bacterial Infections; Clarithromycin; Erythromycin; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Mycobacterium Infections, Nontuberculous; Respiratory Tract Infections; Sexually Transmitted Diseases; Skin Diseases, Infectious

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: Acinetobacter Infections; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Bacteremia; Candidemia; COVID-19 Drug Treatment; Enzyme Inhibitors; Female; Gram-Negative Bacterial Infections; Humans; Hydroxychloroquine; Italy; Klebsiella Infections; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Ventilator-Associated; Protective Factors; Pseudomonas Infections; Respiration, Artificial; SARS-CoV-2; Staphylococcal Infections; Superinfection; Teicoplanin

Gram-negative bacilli are the causative organisms in a significant proportion of patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU). Clinical guidelines recommend broad-spectrum antimicrobials for empirical treatment despite alarming global trends in antimicrobial resistance. In this study, we aimed to assess the safety and efficacy of gentamicin, an aminoglycoside with potent bactericidal activity, for empirical Gram-negative coverage of severe CAP in patients admitted to the ICU. A retrospective cohort study was performed at a university teaching hospital where the severe CAP guideline recommends penicillin, azithromycin and gentamicin as empirical cover. Ceftriaxone plus azithromycin is used as an alternative. Adults with radiologically-confirmed severe CAP were included, comparing those who received gentamicin in the first 72 h of admission with those who did not. Participants were identified using ICD-10 codes for bacterial pneumonia and data manually extracted from electronic medical records. Of 148 patients admitted with severe pneumonia, 117 were given at least one dose of gentamicin whereas the remaining 31 were not. The two groups were well matched in terms of demographics, co-morbidities and disease severity. There were no significant differences between the gentamicin and no-gentamicin groups in the incidence of acute kidney injury [60/117 (51%) vs. 16/31 (52%), respectively], hospital mortality [20/117 (17%) vs. 7/31 (23%)] and secondary outcomes including relapse and length of hospital stay. In conclusion, gentamicin is safe and has similar outcomes to alternative Gram-negative antimicrobial regimens for empirical coverage in severe CAP patients admitted to the ICU.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Community-Acquired Infections; Female; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Pneumonia, Bacterial; Retrospective Studies

The Gram-negative bacillus Stenotrophomonas maltophilia (SM) is an emerging MDR opportunistic pathogen. Recent studies identify a potentially relevant activity of azithromycin against Gram-negative bacteria overlooked in standard bacteriological testing. We investigated azithromycin activity against SM in testing conditions incorporating mammalian tissue culture medium and host defence factors.. MIC testing, chequerboard assays, time-kill assays and fluorescence microscopy were performed for azithromycin, the cationic peptide antibiotic colistin and the human defence peptide cathelicidin LL-37 alone or in combination in cation-adjusted Mueller-Hinton broth or mammalian tissue culture media. Azithromycin sensitization of SM to host immune clearance was tested in a human neutrophil killing assay and a murine pneumonia model.. We observed potent bactericidal activity of azithromycin against SM in mammalian tissue culture medium absent in bacteriological medium. Colistin and LL-37 strongly potentiated azithromycin killing of SM by increasing drug entry. Additionally, azithromycin sensitized SM to neutrophil killing and increased SM clearance in the murine pneumonia model.. Despite lack of activity in standard MIC testing, azithromycin synergizes with cationic peptide antibiotics to kill SM in medium mimicking tissue fluid conditions. Azithromycin, alone or in combination with colistin, merits further exploration in therapy of drug-resistant SM infections.

Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Azithromycin; Cathelicidins; Colistin; Disease Models, Animal; Drug Synergism; Gram-Negative Bacterial Infections; Humans; Mice; Microbial Sensitivity Tests; Neutrophils; Pneumonia, Bacterial; Stenotrophomonas maltophilia; Treatment Outcome

Clonal isolates identified as various nonfermentative Gram-negative bacilli over a 5-year period from sputum cultures of a 30-year-old cystic fibrosis patient were successfully reidentified as Pandoraea sputorum by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Decreased lung function improved after 1 year of azithromycin and inhaled 7%-hypertonic saline treatment.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Burkholderiaceae; Cluster Analysis; Cystic Fibrosis; DNA Fingerprinting; DNA, Bacterial; DNA, Ribosomal; Electrophoresis, Gel, Pulsed-Field; Female; Gram-Negative Bacterial Infections; Humans; Lung; Mass Spectrometry; Molecular Sequence Data; Phylogeny; Respiratory Function Tests; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sputum

The incidence rates of travelers' diarrhea (TD) have remained high for the last 50 years. More recently, there have been increasing recommendations for self-initiated therapy and use of prophylactic drugs for TD. We last examined the in vitro susceptibilities of commonly used antibiotics against TD pathogens in 1997. We now examine 456 enteropathogens isolated from adult travelers to Mexico, India, and Guatemala with diarrhea acquired between 2006 and 2008 to determine changes in susceptibility against 10 different antimicrobials by the agar dilution method. Traditional antibiotics, such as ampicillin, trimethoprim-sulfamethoxazole, and doxycycline, continue to show high levels of resistance. Current first-line antibiotic agents, including fluoroquinolones and azithromycin, showed significantly higher MICs than in our earlier study, and MIC(90) levels were above the Clinical and Laboratory Standards Institute cutoffs for resistance. There were significant geographical differences in resistance patterns when Central America was compared with India. Entertoxigenic Escherichia coli (ETEC) isolates showed increased resistance to ciprofloxacin (P = 0.023) and levofloxacin (P = 0.0078) in India compared with Central America. Enteroaggregative E. coli (EAEC) isolates from Central America showed increased resistance to nearly all of the antibiotics tested. Compared to MICs of isolates 10 years prior, there were 4- to 10-fold increases in MIC(90) values for ceftriaxone, ciprofloxacin, levofloxacin, and azithromycin for both ETEC and EAEC. There were no significant changes in rifaximin MICs. Rising MICs over time imply the need for continuous surveillance of susceptibility patterns worldwide and geographically specific recommendations in TD therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Diarrhea; Drug Resistance, Bacterial; Enterotoxigenic Escherichia coli; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guatemala; Humans; India; Mexico; Microbial Sensitivity Tests; Rifamycins; Rifaximin; Travel

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

Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis. Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones. In this study, MICs of beta-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S. pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies. Rates of resistance to penicillin, azithromycin, and SXT were > or = 7.5% higher among patients < or = 4 years old than among patients 5 to 10, 11 to 17, and > or = 18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons. Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients <18 years old. Levofloxacin MICs of 0.25 to 1 micro g/ml accounted for 99.6, 99.5, 99.3, 99.7, 98.4, and 98.0% of isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old. Multidrug resistance was twice as common among patients < or = 4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and > 64 years old (12.4%). The most common multidrug resistance phenotype in S. pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%). For H. influenzae and M. catarrhalis isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 microg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons. In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S. pneumoniae were susceptible to levofloxacin. If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Moraxella catarrhalis; Ofloxacin; Pneumococcal Infections; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

In this retrospective study, clinical data including clinical manifestations, routine blood tests, chest radiographic imaging from 77 severe cases of SARS treated with integrated Chinese and Western medicine were collected and statistically analyzed. Twenty-nine (37.6%) patients were admitted to the intensive care unit, non-invasive ventilation was used in 40 (51.9%) cases, and invasive ventilatory procedure was performed in eight (10.3%) cases. Seventy (90.9%) patients were clinically cured and seven (9.0%) died. The duration of defervescence was 8.3 +/- 5.0 days after admission. In the early stage, normal leucocyte count was seen in 46 (75.4%) of the 61 patients tested, decreased leucocyte count in 13 (21.3%) and elevated leucocyte count in only two (3.2%) cases. A decreased lymphocyte count was also seen in 23 (37.7%) cases of the 61 patients tested on admission, and by day 14, the number of patients with decreased lymphocyte count (1.11 +/- 0.66 x 10(9)) increased to 32 (47.7%) in 67 cases examined. Neutral granulocyte count was normal or decreased in 58 (95.0%) patients on admission, but elevated from the 7th day onward and peaked on day 21 in 32 (65.3%) of the 49 cases tested. All of the blood abnormalities returned to normal in the convalescent stage. Twenty-nine (37.6%) of the 77 severe cases of SARS patients demonstrated an extensive lung involvement. In comparison with the non-severe SARS cases, this group of patients showed significantly more pneumonic air-space opacities and ground glass-like changes on the chest radiographs (p < 0.05, chi2 test). The role Chinese medicine played in the treatment of SARS was discussed.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Drugs, Chinese Herbal; Female; Fever; Gram-Negative Bacterial Infections; Humans; Leukocyte Count; Male; Middle Aged; Prognosis; Radiography; Respiration, Artificial; Retrospective Studies; Severe Acute Respiratory Syndrome; Severity of Illness Index

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cefuroxime; Cephalosporins; Gram-Negative Anaerobic Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Pneumonia

In Vitro and in vivo antibacterial activities of azithromycin were compared with those of macrolides and other antimicrobial agents. In the in vitro activity azithromycin has a potent activity against both gram-positive and gram-negative bacteria, but against the latter organisms the other macrolides have little potent activity. The in vitro results demonstrate that azithromycin has a high potent activity against respiratory pathogens such as erythromycin-susceptible staphylococci, streptococci (except for organisms possessing erm gene), H, influenzae, B. prtussis, Legionella spp., M. pneumoniae, C. trachomatis. In the pharmacokinetic of azithromycin in mice, it is found that its half life is longer than the other macrolides and the concentration of it in polymorphonuclear leukocytes and lung tissues is higher than the other macrolides. These specific properties in the pharmacodynamic and the in vitro antibacterial activities reflect the therapeutic efficacies in experimental infection models. Finally, the therapeutic efficacies of azithromycin in various infection models better than those of the other macrolides.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cells, Cultured; Cricetinae; Disease Models, Animal; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guinea Pigs; Half-Life; Humans; Lung; Mice; Neutrophils