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Antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia.

OBJECTIVES: To characterise comprehensively the antibiotic susceptibility of Neisseria gonorrhoeae in Arkhangelsk, Russia, and to investigate whether the recommended treatment guidelines are updated and effective. METHODS: The susceptibility of N gonorrhoeae isolates, cultured during June-November 2004 mainly from consecutive patients with gonorrhoea (n = 76) in Arkhangelsk, to penicillin G, ampicillin, cefixime, ceftriaxone, ciprofloxacin, erythromycin, azithromycin, kanamycin, spectinomycin and tetracycline was analysed using Etest. Nitrocefin discs were used for beta-lactamase detection. RESULTS: The levels of intermediate susceptibility and resistance to the different antibiotics were as follows: penicillin G 76%, ampicillin 71%, cefixime 0%, ceftriaxone 3%, ciprofloxacin 17%, erythromycin 54%, azithromycin 14%, kanamycin 49%, spectinomycin 0% and tetracycline 92%. Of the isolates 55 (72%) were determined as multiresistant--that is, they showed intermediate susceptibility or resistance to three or more classes of antibiotics. However, none of the isolates were beta-lactamase producing. CONCLUSIONS: In Arkhangelsk, and presumably in many other areas of Russia, penicillins, ciprofloxacin, erythromycin, azithromycin, kanamycin and tetracycline should not be used in the treatment of gonorrhoea if the results of antibiotic susceptibility testing are not available. In Russia, optimised, standardised and quality-assured antibiotic susceptibility testing needs to be established in many laboratories. Subsequently, continuous local, regional and national surveillance of antibiotic susceptibility is crucial to detect the emergence of new resistance, monitor changing patterns of susceptibility and be able to update treatment recommendations on a regular basis.

Adolescent↗

Macrolides inhibit epithelial cell-mediated neutrophil survival by modulating granulocyte macrophage colony-stimulating factor release.

Macrolides have been shown to be effective in treating diffuse panbronchiolitis (DPB), although the precise modes of action remain unclear. At sites of airway inflammation, respiratory epithelium is considered an active participant in regulating neutrophil survival. We therefore examined the effect of erythromycin, clarithromycin, azithromycin, and josamycin on both neutrophil survival and on epithelial-derived factors, which influence neutrophil longevity. Media conditioned with transiently tumor necrosis factor (TNF)-alpha-stimulated A549 human airway epithelial cells prolonged neutrophil survival compared with control media. The presence of dexamethasone during neutrophil culture led to further prolongation of neutrophil survival. In contrast, none of the tested macrolides modulated neutrophil survival, suggesting a lack of direct effect of these drugs. On the other hand, pretreatment of TNF-alpha-stimulated A549 cells by erythromycin, clarithromycin, azithromycin, or dexamethasone, but not josamycin, decreased the neutrophil survival-enhancing effects in a dose-dependent manner. Neutralizing antibodies to granulocyte macrophage colony-stimulating factor (GM-CSF) dampened the prolonged neutrophil survival observed in TNF-alpha-stimulated A549 conditioned media. Erythromycin, clarithromycin, azithromycin, and dexamethasone inhibited TNF-alpha-induced GM-CSF expression in A549 cells at both the protein and messenger RNA levels. These results suggest that macrolides inhibit epithelial cell-mediated neutrophil survival by modulating GM-CSF release, which may, at least in part, explain the effectiveness of this family of drugs on DPB.

Antibodies↗

Macrolides in cystic fibrosis.

Macrolide antibiotics have been licensed since the 1950s and have an important role in the treatment of a diverse range of infectious diseases. Macrolide antibiotics have antibacterial activity against gram-positive bacteria, some gram-negative bacteria and intracellular pathogens. The spectrum of antibacterial activity combined with excellent intracellular and tissue penetration has led to the extensive use of this class of drugs in respiratory disease. Macrolide antibiotics also have demonstrated anti-inflammatory properties in various in vitro and in vivo model systems. Novel antimicrobial and anti-inflammatory properties of macrolide may result in clinical benefits, particularly in conditions where the infectious agent is inherently resistant to macrolides. Three randomized control trials have demonstrated improved lung function in patients treated with the macrolide antibiotic, azithromycin. Azithromycin was generally well tolerated and resulted in reduction in the inflammatory response which may be due to an immunomodulatory role. Short term studies (three to six months) have not demonstrated the development of increased bacterial resistance or the emergence of new pathogens following azithromycin.

Anti-Bacterial Agents↗

Macrolide drug interactions: an update.

OBJECTIVE: To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions. DATA SOURCES: A MEDLINE search (1975-1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers. STUDY SELECTION: All available data were reviewed to provide an unbiased account of possible drug interactions. DATA EXTRACTION: Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. DATA SYNTHESIS: Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides. CONCLUSIONS: Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.

Anti-Bacterial Agents↗

Clinical pharmacokinetic properties of the macrolide antibiotics. Effects of age and various pathophysiological states (Part I).

The pharmacokinetic aspects in humans of macrolide antibiotics that are currently or soon to be on the market (i.e. erythromycin, oleandomycin, spiramycin, josamycin, midecamycin, miocamycin, rosaramycin, roxithromycin and azithromycin) are reviewed. Macrolide antibiotics are basic compounds, poorly soluble in water, which are mostly absorbed in the alkaline intestinal environment. They are acid unstable, but the newer semisynthetic derivatives (i.e. roxithromycin and azithromycin) are characterised by increased stability under acidic conditions. Macrolides are highly liposoluble and consequently penetrate well into tissue, especially bronchial secretions, prostatic tissue, middle ear exudates and bone tissues, as evidenced by tissue/serum concentration ratios greater than 1. They do not penetrate well into the CSF. Macrolides undergo extensive biotransformation in the liver. With a few exceptions (e.g. miocamycin), the metabolites of these drugs are characterised by little or no antimicrobial activity. Plasma protein binding is variable from one compound to another. At therapeutic concentrations, protein-bound erythromycin accounts for 80 to 90% of the total drug present in the blood, and the fraction is 95% for roxithromycin. The lowest values of protein-bound fraction are observed for midecamycin and josamycin (about 15%), and intermediate values are reported for spiramycin and miocamycin. However, the clinical relevance of this parameter is not clearly established. Plasma half-life (t1/2) values vary for the macrolides described: erythromycin, oleandomycin, josamycin and miocamycin have a t1/2 ranging from 1 to 2 hours; spiramycin, erythromycin stearate, the mercaptosuccinate salt of propionyl erythromycin and rosaramicin have an intermediate t1/2 (about 7, 6.5, 5 and 4.5 hours, respectively); the newer semisynthetic compounds roxithromycin and azithromycin are characterised by high t1/2 values (i.e. 11 and 41 hours, respectively). Under normal conditions, the major route of elimination is the liver. Renal elimination also takes place but it contributes to total clearance only to a small degree, as evidenced by low renal clearance values. The degree of modification of macrolide pharmacokinetics by renal insufficiency or hepatic disease is usually not considered clinically relevant, and no recommendation for dose modification is necessary in these patients. The pharmacokinetics of macrolides are modified in elderly patients. Accordingly, their use must be accompanied by a closer than usual clinical monitoring of the older patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

The role of advanced generation macrolides in the prophylaxis and treatment of Mycobacterium avium complex (MAC) infections.

Since the start of the acquired immunodeficiency syndrome (AIDS) epidemic, the role of Mycobacterium avium complex (MAC) as an opportunistic pathogen in advanced AIDS patients has become more and more clear. Once identified in an advanced AIDS patient it is possible to find evidence that the MAC organism and infection is not only present in the pulmonary tree, but has also disseminated to a wide variety of body organs. Treatment of MAC or disseminated MAC (DMAC) infections has historically been very difficult due to the inherent resistance of the MAC pathogen to most standard antimycobacterial agents. This has resulted in the development of new agents for the prevention of DMAC infection as well as combinations of both new and standard agents for its treatment. Three drugs are currently approved for single-agent DMAC prophylaxis, including rifabutin, azithromycin and clarithromycin. Combinations of agents for DMAC treatment are highly variable in content but most experts agree that all combinations should contain one of the advanced generation macrolides (azithromycin or clarithromycin). Both of these agents have favourable intracellular pharmacokinetics and pharmacodynamics which maximise their effects against this mostly intracellular pathogen. Due to the paucity of comparative data, no one macrolide can be recommended over the other. However, the expected increase in compliance, lower weekly and annual costs, and lack of any drug interactions may make azithromycin a preferable choice, but this should be decided on a case-by-case basis.

Anti-Bacterial Agents↗

Short-course antimicrobial therapy of respiratory tract infections.

Accumulating evidence suggests that short-course (</=5 days, </=3 days for azithromycin) antimicrobial therapy may be at least as effective as and, in some cases, may be more effective than traditional longer (10- to 14-day) therapies. In group A beta-haemolytic streptococcal tonsillopharyngitis, short-course therapy with 6 days of amoxicillin, 4-5 days of a variety of cephalosporins and 5 days of clarithromycin modified-release and telithromycin are all reasonable alternatives to traditional 10-day penicillin therapy. Short-course (i.e. 3-day) azithromycin therapy is not recommended because of suboptimal clinical and bacteriological results compared with penicillin therapy, unless the dosage is doubled from 10 to 20 mg/kg/day for all 3 days. In uncomplicated acute suppurative otitis media, single-dose intramuscular ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be effective in the majority (>/=80%) of patients. However, more research is clearly needed in the subpopulations of children <2 years of age and in those with unresponsive/recurrent disease, since short-course therapy may not be successful in the majority of these patients. In sinusitis, most short-course therapy data have involved maxillary disease in adult patients. Regimens have included 3 days of azithromycin or cotrimoxazole (trimethoprim/sulfamethoxazole) or 5 days of cefpodoxime, telithromycin, gatifloxacin, gemifloxacin or amoxicillin/clavulanic acid. Preliminary results are encouraging but more study is clearly needed, especially in the paediatric population. In acute bacterial exacerbations of chronic bronchitis, short-course therapy with a variety of cephalosporins, second-generation fluoroquinolones and advanced generation macrolides/azalides/ketolides are all reasonable alternatives to traditional 7- to 14-day therapies. Cost containment in antimicrobial therapy should involve consideration of short-course therapy in the management of the most common types of respiratory tract infections.

Anti-Bacterial Agents↗

Treatment of Legionnaires' disease.

Legionnaires' disease is pneumonia, usually caused by Legionella pneumophila, which can range in severity from mild to quite severe. While it is commonly acquired in the community, it can just as easily be acquired nosocomially from water sources that have not been appropriately decontaminated. While historically initial treatment was always with erythromycin, current case series and treatment recommendations suggest that outpatients receive immediate treatment with one of the following antibacterials: azithromycin, erythromycin, clarithromycin, telithromycin, doxycycline or an extended-spectrum fluoroquinolone. If the symptoms are severe enough to warrant hospitalisation then the patient should receive treatment with parenteral azithromycin or extended-spectrum fluoroquinolones followed by step-down to oral formulations to complete the regimens. While a shorter course of 7-10 days for more severe infections may be possible for intravenous/oral azithromycin, other antibacterials should be administered for a total of 10-21 days and started as soon as possible upon presentation to optimise outcomes.

Anti-Bacterial Agents↗

Economic evaluation of antibacterials in the treatment of acute sinusitis.

OBJECTIVE: The objective of this study was to compare costs, efficacy and cost efficacy of alternate oral antibacterial regimens for the ambulatory treatment of acute sinusitis. A public third-party perspective was adopted. DESIGN: The analysis was based on a decision tree and considered the episode of care from the decision to initiate an antibacterial until the end of the first course of treatment or the end of a subsequent course of treatment when needed. Efficacy data were retrieved from published clinical trials. Direct medical costs included the costs of physician visits, diagnostic tests and medications. SETTING: The study pertained to adults treated in a primary-care setting in the Canadian province of Québec. INTERVENTIONS: The antibacterials studied were amoxicillin, amoxicillin/clavulanate, azithromycin, cefaclor, cefuroxime axetil and clarithromycin. MAIN OUTCOME MEASURES AND RESULTS: The main outcome measured was the proportion of patients showing resolution or improvement of their symptoms. Initiating a treatment with amoxicillin was associated with similar efficacy and lower overall costs when compared with the other antibacterials. Low dosages of clarithromycin and azithromycin followed amoxicillin in terms of cost-efficacy ratio. CONCLUSIONS: This study confirms the place of amoxicillin as a first choice agent for acute sinusitis, with low dose clarithromycin and azithromycin as second choices.

Acute Disease↗

A guide to selection and appropriate use of macrolides in skin infections.

Dermatologists must be aware of the adverse effects of antimicrobial agents as well as various drug interactions that may influence the choice of drug as well as specific drug schedules. The development of modern antibacterials has improved the treatment of cutaneous bacterial infections. Macrolide antibacterials continue to be an important therapeutic class of drugs with established efficacy in a variety of skin infections. All macrolides inhibit protein synthesis by reversibly binding to the 23S ribosomal RNA in the 50S-subunit. Erythromycin, the prototype of macrolide antibacterials, was isolated from the metabolic products of a strain of Streptomyces erytherus in 1952. Originally, erythromycin was introduced as an alternative to penicillin because of its activity against the Gram-positive organisms. Numerous studies have demonstrated the efficacy and safety of erythromycin for various infectious diseases. Unfortunately, erythromycin is associated with a number of drawbacks including a narrow spectrum of activity, unfavorable pharmacokinetic properties, poor gastrointestinal tolerability, and a significant number of drug-drug interactions. Newer macrolides have been developed to address these limitations. The pharmacokinetics of azithromycin and clarithromycin allow for shorter dosing schedules because of prolonged tissue levels. The efficacy of azithromycin for the treatment of skin and soft tissue infections in adults and children is well established. The unique pharmakinetics of azithromycin makes it a suitable agent for the treatment of acne. Clarithromycin represents a clear advance in the macrolide management of patients with leprosy and skin infections with atypical mycobacteria. Dirithromycin and roxithromycin display no clinical or bacteriological adcantage over erythromycin despite a superior pharmacokinetic profile. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens which may limit the clinical usefulness of this class of antimicrobial agents in future.

Anti-Bacterial Agents↗

Drug treatment of nonviral sexually transmitted diseases: specific issues in adolescents.

Sexually transmitted diseases (STDs) are common and happen more frequently in younger patients. These adolescents have unique risks of acquiring infection because of developing psychosocial skills, biological factors and sociocultural barriers. The clinician must be adept at identifying and modifying these risks through knowledge of the adolescent stages of development and biology, with good history and examination skills that make teens comfortable during their evaluation, and with patient education and treatment. Whereas patient compliance and partner notification can be problematic in any population, teenagers may be more prone not to follow through on these issues. While compliance may notbe as important as previously thought, there is a dearth of studies of patient compliance and STD treatment in adolescents. Guidelines for the treatment of STDs were published by the Centers for Disease Control and Prevention (CDC) in 1998 and the Medical Society for the Study of Venereal Diseases in 1999. Most of the data obtained to formulate these guidelines were not necessarily adolescent specific and few studies, if any, have included adolescent patients since the CDC document was published. In the treatment of chlamydia, it appears that even with relative noncompliance with the 7-day regimen of doxycycline, it is as effective as single dose azithromycin. This has implications in cost control, important for centres with limited funds for treatment. While fluoroquinolone-resistant gonorrhoea has been reported for some time, the number of reports in the US is increasing, with a recent report of decreased susceptibility to azithromycin. As many studies have shown efficacy with single agent therapy with azithromycin in combined gonococcal and chlamydial infection, one must view these new resistance data with concern and give serious consideration to dual agent treatment, especially in the locale of the practitioner. Also, fluoroquinolone use is not advised in patients under the age of 18 years at present because of concerns of adverse effects on cartilage. While not much has changed from the 1998 guidelines for most of the other STDs, there seems to be a general trend in treating pelvic inflammatory disease (PID) on an outpatient basis if good follow-up is assured, even in the adolescent population. There is still debate on whether anaerobe coverage is needed in PID without tubo-ovarian abscess or other complications. One other update includes the use of daily metronidazole gel instead of twice daily usage in the treatment of bacterial vaginosis. With the lack of studies specific to adolescents, it is left up to the clinician to tailor the treatment of adolescents on the basis of current guidelines and patient preferences.

Adolescent↗

Effects of macrolides and ketolides on mycobacterial infections.

New macrolides, such as clarithromycin and azithromycin, are active agents to Mycobacterium avium complex (MAC). Both clarithromycin and azithromycin are well-known for the ability to improve the prognosis of AIDS patients with disseminated MAC infection. However, the administration of monotherapy with a macrolide is usually associated with the emergence of drug resistance after a few months of use. Therefore, the recommended treatment for MAC infection involved the use of at least two antibiotics, which includes a macrolide in combination with rifabutin, moxifloxacin and/or ethambutol. When used as prophylactic therapy in AIDS patients, azithromycin is more convenient (1200 mg, once a week) than clarithromycin (500 mg, twice a day). Ketolides are a semi-synthetic derivative of erythromycin A, which differs from erythromycin A by substitution of a 3-keto group for L-cladinose. Telithromycin has a carbamate group linked to an imidazolium and pyridium nucleus at C11-C12. In mice model, both telithromycin and ABT-733 were active in vivo against MAC.

Animals↗

Oral antimicrobial susceptibilities of Streptococcus pyogenes recently isolated in five countries.

Between July 1998 and July 1999 1050 clinical isolates of Streptococcus pyogenes were collected from 11 study centres in five countries. Isolates were shipped to a co-ordinating laboratory for NCCLS specified broth microdilution susceptibility testing for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin and roxithromycin. All 1050 isolates of S. pyogenes tested were susceptible to penicillin (MIC < or = 0.12 microgram/ml) and cefaclor (MIC < or = 0.25 microgram/ml). Azithromycin, clarithromycin and erythromycin resistance rates were 15.9%, 15.4% and 15.8%, respectively. MIC90S for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin, and roxithromycin were 0.015, 0.12, > 4, 8, > 1 and 16 micrograms/ml, respectively. Macrolide (erythromycin) resistance rates were highest in study centres in Italy (31.0%) and Spain (26.6%). Lower macrolide resistance rates were identified in study centres in Turkey (4.8%), France (3.8%), and Sweden (3.7%). In conclusion, the isolates of S. pyogenes tested were universally susceptible to beta-lactam antibiotics such as penicillin and cefaclor, while resistance to macrolides was significant and ranged from 3.2% to 31%.

Anti-Bacterial Agents↗

Microbiological profile of telithromycin, the first ketolide antimicrobial.

Telithromycin, the first of the ketolide antimicrobials, has been specifically designed to provide potent activity against common and atypical/intracellular or cell-associated respiratory pathogens, including those that are resistant to beta-lactams and/or macrolide-lincosamide-streptograminB (MLS(B)) antimicrobials. Against gram-positive cocci, telithromycin possesses more potent activity in vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains its activity against erm-(MLS(B)) or mef-mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLS(B) mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, regardless of beta-lactamase production. In vitro, it shows similar activity to azithromycin against H. influenzae, while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. In vitro, telithromycin does not induce MLS(B) resistance and it shows low potential to select for resistance or cross-resistance to other antimicrobials. These characteristics indicate that telithromycin will have an important clinical role in the empirical treatment of community-acquired respiratory tract infections.

Anti-Bacterial Agents↗

E test for studying in vitro activity of seven antimicrobial agents against penicillin-susceptible and penicillin-resistant pneumococci.

OBJECTIVE: To evaluate the comparative activity of seven oral antimicrobial agents against 100 strains of Streptococcus pneumoniae (S. pneumoniae). METHODS: Total 100 strains of S. pneumoniae were collected from general hospitals in Beijing from June 1996 to June 1997. E test method was used to detect the minimum inhibitory concentration (MIC) values of the following seven drugs against S. pneumoniae: penicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, ceftriaxone, azithromycin and ofloxacin. The breakpoint of susceptibility categories was defined according to NCCLS. RESULTS: 74% of isolates were susceptible (S, MIC 0.06 mg/L) to penicillin, and 5% were penicillin resistant (R, MIC 2 mg/L). The intermediately resistant (I, MIC 0.1-1 mg/L) rate to penicillin was 21%. The total rates of R or I were 26% for penicillin, 6% for both amoxicillin/clavulanate and ceftriaxone, 9% for cefuroxime, 66% and 68% for azithromycin and ofloxacin respectively. Overall 94%, 94% and 91% of the pneumococcal isolates were susceptible to amoxicillin/clavulanate, ceftriaxone and cefuroxime respectively. S. pneumoniae was highly resistant to azithromycin tested as a representative of macrolides (MIC50 and MIC90 both > 256 mg/L, R rate 66%), and had a highly intermediately resistant rate to ofloxacin (I rate 62%). CONCLUSIONS: Our data suggest that in vitro activity of oral amoxicillin/clavulanate was as good as ceftriaxone and cefuroxime. It can be considered as an alternative compound in the treatment of community acquired pneumoniae and other respiratory tract infections caused by multiresistant S. pneumoniae.

Amoxicillin↗

[Efficacy of some new antibiotics in treating experimental brucellosis].

Brucella pathogens are highly susceptible in vitro to pefloxacin, lomefloxacin, meropenem and azithromycin. High efficacy of these drugs was demonstrated for experimental brucellosis treatment, azithromycin being the most active. Meropenem and azithromycin implementation resulted in more rapid and full normalization of the bactericidial and energy systems of the experimental animals peripheral blood cells.

Animals↗

[The etiology of bacterial respiratory infections in adulthood].

Upper and lower respiratory tract infections are the most frequently reported pathologies both in children and in adults. In particular, the most common clinical pictures are otitis media, principally chronic, and acute and chronic sinusitis. The microbiology of otitis media, which has been investigated thoroughly in the last year, confirmed a bacterial origin in 90% of the cases (while the incidence of the viral form is low). The etiologic agents responsible for chronic infections are Gram-negative bacteria, staphylococci and anaerobic bacteria, while in the acute forms, which are rare in adults but frequent in children, the responsible pathogens are principally Haemophilus influenzae, Streptococcus pyogenes and Branhamella catarrhalis. Among the etiologic agents of chronic sinusitis, which, from a clinical point of view, is the most frequently observed, there are staphylococci, Streptococcus pyogenes and many anaerobic bacteria. As regards lower respiratory tract infections, chronic bronchitis is the most frequent pathology in adults. But, in this case, the etiologic agents are more difficult to identify. Analysing the above-mentioned clinical pictures and their relevant etiologic agents, among the different therapeutic proposals, one of the most innovative and recent is represented by azithromycin. Azithromycin is the first of a new class of macrolides termed "Azalides" which shows particular microbiological and pharmacokinetic characteristics. As compared to other macrolides, it has an higher distribution volume, a longer half-life, a deeper intracellular penetration and a wider spectrum of action. It is rapidly concentrated in leukocytes PMN, monocytes, macrophages and fibroblasts and slowly released by these cells to the infected tissues. Azithromycin concentrations in tissues and sites of infection can be increased by the phagocyte uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Meta-analysis of clarithromycin compared to other antibiotics for the treatment of lower respiratory tract infections].

Clarithromycin is a macrolide antibiotic commonly used for the treatment of respiratory infections. The aim of this study was to assess its effectiveness for the treatment of lower respiratory tract infections. A number of meta-analyses of clinical trials comparing clarithromycin to the antibiotics most frequently used in the treatment of lower respiratory tract infections, such as cephalosporins, amoxicillin-clavulanic acid, erythromycin and azithromycin, have been performed. Clarithromycin's effectiveness for the treatment of lower respiratory tract infections was better than that for cephalosporins (OR = 1.43; 95% CI = 1.09-1.86) and, although not to the same extent, that for amoxicillin-clavulanic acid (OR = 1.58; 95% CI = 0.92-2.70); however, the efficacy was only similar to that shown for azithromycin (OR = 0.57; 95% CI = 0.19-1.68). The fourth meta-analysis compared the effectiveness of clarithromycin to that of erythromycin for the treatment of pneumonia and showed a superior odds ratio in favor of clarithromycin (OR = 1.46; 95% CI = 0.97-2.2). Meta-analyses comparing clarithromycin's safety to that of the same drugs in the same conditions used in the assessment of effectiveness showed a similar incidence of adverse events compared to amoxicillin-clavulanic acid, and azithromycin, a slightly lower incidence compared to erythromycin, and a slightly higher incidence compared to cephalosporins. In conclusion, these meta-analyses show that clarithromycin is an effective and safe antibiotic for the treatment of lower respiratory tract infections. Furthermore, a new once-daily dose formulation with a positive impact on therapeutic compliance is currently available, making clarithromycin a first-line treatment for lower respiratory tract infections.

Anti-Bacterial Agents↗