Ketolides
Macrolides
Erythromycin
Roxithromycin
Microbial Sensitivity Tests
Naphthyridines
Drug Resistance, Bacterial
Moraxella (Branhamella) catarrhalis
Azithromycin
RNA, Ribosomal, 23S
Streptococcus pneumoniae
Respiratory Tract Infections
Drug Resistance, Microbial
RNA, Ribosomal
Staphylococcus
Ketolide treatment of Haemophilus influenzae experimental pneumonia. (1/299)
The MICs of HMR 3004 and HMR 3647 at which 90% of beta-lactamase-producing Haemophilus influenzae isolates were inhibited were 4 and 2 micrograms/ml, respectively. Both HMR 3004 and HMR 3647 were active against beta-lactamase-producing H. influenzae in a murine model of experimental pneumonia. As assessed by pulmonary clearance of H. influenzae, HMR 3004 was more effective (P < 0.05) than was azithromycin, ciprofloxacin, clarithromycin, erythromycin A, pristinamycin, or HMR 3647 in this model. (+info)The in-vitro activity of HMR 3647, a new ketolide antimicrobial agent. (2/299)
The in-vitro activity of HMR 3647, a novel ketolide, was investigated in comparison with those of erythromycin A, roxithromycin, clarithromycin (14-membered ring macrolides), amoxycillin-clavulanate and ciprofloxacin against 719 recent clinical Gram-positive, Gram-negative and anaerobic isolates and type cultures. HMR 3647 generally demonstrated greater activity than the other compounds with MIC90s of < or =0.5 mg/L, except for Staphylococcus epidermidis (MIC90 > 128 mg/L), Haemophilus influenzae (MIC90 = 2 mg/L), Enterococcus faecalis (MIC90 = 2 mg/L), Enterococcus faecium (MIC90 = 1 mg/L) and the anaerobes, Bacteroides fragilis (MIC90 = 2 mg/L) and Clostridium difficile (MIC90 = 1 mg/L). In general, an increase in the size of the inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs of HMR 3647. Additionally, the in-vitro activity of HMR 3647 was not affected by the presence of either 20 or 70% (v/v) human serum. The antichlamydial activity of HMR 3647 was generally greater than that of commonly used antichlamydial antimicrobials. (+info)In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria. (3/299)
The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (EMs), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 microgram/ml; range, 0.03 to 0.06 microgram/ml; MIC50 [erythromycin], 0.25 microgram/ml; range, 0.25 to 0.5 microgram/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 micrograms/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC < or = 0.5 microgram/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 micrograms/ml were 0.015 microgram/ml. E. faecalis strains that had erythromycin MICs of 128 to > 512 micrograms/ml showed HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml. In the group of E. faecium strains for which MICs of erythromycin were > or = 512 micrograms/ml, MICs of both ketolides were in the range of 1 to 64 micrograms/ml, with almost all isolates showing ketolide MICs of < or = 16 micrograms/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted. (+info)In vitro activities of ketolides HMR 3647 [correction of HRM 3647] and HMR 3004 [correction of HRM 3004], levofloxacin, and other quinolones and macrolides against Neisseria spp. and Moraxella catarrhalis. (4/299)
In vitro activities of the ketolides HMR 3647 [corrected] and HMR 3004 [corrected] against pathogenic Neisseria gonorrhoeae and N. meningitidis, saprophytic Neisseria isolates, and Moraxella catarrhalis were determined. The comparison of ketolide activities with those of the other macrolides shows a much better activity in the majority of species, with macrolide MICs at which 90% of the isolates are inhibited between 8- and 10-fold higher. (+info)The effects of ketolides on bioactive phospholipid-induced injury to human respiratory epithelium in vitro. (5/299)
The potential of the novel ketolide antimicrobial agents, HMR 3004 and HMR 3647, to antagonize the injurious effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the ciliary beat frequency and structural integrity of human ciliated respiratory epithelium in vitro was investigated, in the presence or absence of polymorphonuclear leukocytes (PMNL). The ciliary beat frequency of human nasal respiratory epithelium, obtained by nasal brushing of healthy volunteers, was measured using a photo-transistor technique, while superoxide generation by activated human PMNL and membrane-stabilizing activity were measured by lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL, at concentrations of 2.5 microg x mL(-1), caused significant (p<0.005) ciliary slowing and epithelial damage, while treatment of the epithelial strips with the ketolides, in particular HMR 3004, caused dose-related attenuation of these direct adverse effects of the PL on ciliated epithelium, apparently by a membrane-stabilizing mechanism. When epithelial strips were exposed to the combination of PMNL (1 x 10(6) cells x mL(-1)) and PAF (1 microg x mL(-1)), significant ciliary dysfunction and epithelial damage were also observed, which were mediated predominantly by neutrophil-derived oxidants. These injurious effects of PAF were antagonized by preincubation of the epithelial strips or the PMNL with HMR 3004 (10 microg x mL(-1)). The ketolide antimicrobial agents, in particular HMR 3004, antagonize the direct and polymorphonuclear leukocyte-mediated injurious effects of phospholipids on human ciliated epithelium and may have beneficial effects in inflammatory disorders of the airways, such as asthma, chronic bronchitis, diffuse panbronchiolitis and bronchiectasis. (+info)Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology. (6/299)
Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC /=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred. (+info)The new ketolide HMR3647 accumulates in the azurophil granules of human polymorphonuclear cells. (7/299)
HMR3647 is a semisynthetic representative of a new group of drugs, the ketolides, derived from erythromycin A. Since macrolides have been shown to accumulate in human polymorphonuclear cells (PMNs), we have investigated the ability of the molecule HMR3647 to enter human PMNs as well as other cell types, such as peripheral blood mononuclear cells and cell lines of hematopoietic and nonhematopoietic origin. In these experiments, HMR3647 was compared to erythromycin A, azithromycin, clarithromycin, and roxithromycin. Our results show that HMR3647 is specifically trapped in PMNs, where it is concentrated up to 300 times. In addition, it is poorly released by these cells, 80% of the compound remaining cell associated after 2 h in fresh medium. By contrast, it is poorly internalized and quickly released by the other cell types studied. This differs from the results obtained with the macrolide molecules, which behaved similarly in the different cells studied. In addition, subcellular fractionation of PMNs allowed us to identify the intracellular compartment where HMR3647 was trapped. In PMNs, more than 75% of the molecule was recovered in the azurophil granule fraction. Similarly, in NB4 cells differentiated into PMN-like cells, almost 60% of the molecules accumulated in the azurophil granule fraction. In addition, when HMR3647 was added to disrupted PMNs, 63% accumulated in the azurophil granules. Therefore, this study shows that the ketolide HMR3647 specifically accumulates in PMN azurophil granules, thus favoring its delivery to bacteria phagocytosed in these cells. (+info)Activities of telithromycin (HMR 3647, RU 66647) compared to those of erythromycin, azithromycin, clarithromycin, roxithromycin, and other antimicrobial agents against unusual anaerobes. (8/299)
The comparative activity of telithromycin (HMR 3647) against 419 human anaerobic isolates was determined by the agar dilution method. At concentrations of +info)Ketolides are a class of antibiotics, which are chemically modified versions of macrolide antibiotics. They have an extended spectrum of activity and improved stability against bacterial resistance mechanisms compared to older macrolides. Ketolides inhibit protein synthesis in bacteria by binding to the 50S ribosomal subunit.
The main ketolide antibiotics include telithromycin, cethromycin, and solithromycin. They are primarily used for treating respiratory tract infections caused by susceptible strains of bacteria, including drug-resistant pneumococci and atypical pathogens like Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia pneumoniae.
It is important to note that ketolides have potential side effects, such as gastrointestinal disturbances, liver enzyme elevations, and cardiac arrhythmias, which should be considered when prescribing them.
Macrolides are a class of antibiotics derived from natural products obtained from various species of Streptomyces bacteria. They have a large ring structure consisting of 12, 14, or 15 atoms, to which one or more sugar molecules are attached. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit, thereby preventing peptide bond formation. Common examples of macrolides include erythromycin, azithromycin, and clarithromycin. They are primarily used to treat respiratory, skin, and soft tissue infections caused by susceptible gram-positive and gram-negative bacteria.
Erythromycin is a type of antibiotic known as a macrolide, which is used to treat various types of bacterial infections. It works by inhibiting the bacteria's ability to produce proteins, which are necessary for the bacteria to survive and multiply. Erythromycin is often used to treat respiratory tract infections, skin infections, and sexually transmitted diseases. It may also be used to prevent endocarditis (inflammation of the lining of the heart) in people at risk of this condition.
Erythromycin is generally considered safe for most people, but it can cause side effects such as nausea, vomiting, and diarrhea. It may also interact with other medications, so it's important to tell your doctor about all the drugs you are taking before starting erythromycin.
Like all antibiotics, erythromycin should only be used to treat bacterial infections, as it is not effective against viral infections such as the common cold or flu. Overuse of antibiotics can lead to antibiotic resistance, which makes it harder to treat infections in the future.
Roxithromycin is a macrolide antibiotic that is used to treat various types of bacterial infections, including respiratory tract infections, skin and soft tissue infections, and sexually transmitted diseases. It works by inhibiting the growth of bacteria by interfering with their protein synthesis.
Roxithromycin has a broad spectrum of activity against both Gram-positive and Gram-negative bacteria, including Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia trachomatis, and Neisseria gonorrhoeae.
The drug is available in various forms, including tablets, capsules, and oral suspension, and is usually taken twice a day for 5-10 days, depending on the type and severity of the infection being treated. Common side effects of roxithromycin include nausea, diarrhea, abdominal pain, headache, and skin rash.
It's important to note that roxithromycin should only be used under the guidance of a healthcare professional, as with any medication, to ensure its safe and effective use.
Anti-bacterial agents, also known as antibiotics, are a type of medication used to treat infections caused by bacteria. These agents work by either killing the bacteria or inhibiting their growth and reproduction. There are several different classes of anti-bacterial agents, including penicillins, cephalosporins, fluoroquinolones, macrolides, and tetracyclines, among others. Each class of antibiotic has a specific mechanism of action and is used to treat certain types of bacterial infections. It's important to note that anti-bacterial agents are not effective against viral infections, such as the common cold or flu. Misuse and overuse of antibiotics can lead to antibiotic resistance, which is a significant global health concern.
Microbial sensitivity tests, also known as antibiotic susceptibility tests (ASTs) or bacterial susceptibility tests, are laboratory procedures used to determine the effectiveness of various antimicrobial agents against specific microorganisms isolated from a patient's infection. These tests help healthcare providers identify which antibiotics will be most effective in treating an infection and which ones should be avoided due to resistance. The results of these tests can guide appropriate antibiotic therapy, minimize the potential for antibiotic resistance, improve clinical outcomes, and reduce unnecessary side effects or toxicity from ineffective antimicrobials.
There are several methods for performing microbial sensitivity tests, including:
1. Disk diffusion method (Kirby-Bauer test): A standardized paper disk containing a predetermined amount of an antibiotic is placed on an agar plate that has been inoculated with the isolated microorganism. After incubation, the zone of inhibition around the disk is measured to determine the susceptibility or resistance of the organism to that particular antibiotic.
2. Broth dilution method: A series of tubes or wells containing decreasing concentrations of an antimicrobial agent are inoculated with a standardized microbial suspension. After incubation, the minimum inhibitory concentration (MIC) is determined by observing the lowest concentration of the antibiotic that prevents visible growth of the organism.
3. Automated systems: These use sophisticated technology to perform both disk diffusion and broth dilution methods automatically, providing rapid and accurate results for a wide range of microorganisms and antimicrobial agents.
The interpretation of microbial sensitivity test results should be done cautiously, considering factors such as the site of infection, pharmacokinetics and pharmacodynamics of the antibiotic, potential toxicity, and local resistance patterns. Regular monitoring of susceptibility patterns and ongoing antimicrobial stewardship programs are essential to ensure optimal use of these tests and to minimize the development of antibiotic resistance.
Naphthyridines are a class of heterocyclic organic compounds that contain a naphthyridine core structure, which is a polycyclic aromatic hydrocarbon made up of two benzene rings fused to a tetrahydropyridine ring. They have a variety of pharmacological activities and are used in the development of various therapeutic agents, including antibiotics, antivirals, and anticancer drugs.
In medical terms, naphthyridines do not have a specific clinical definition or application, but they are rather a chemical class that is utilized in the design and synthesis of drugs with potential therapeutic benefits. The unique structure and properties of naphthyridines make them attractive candidates for drug development, particularly in areas where new treatments are needed to overcome drug resistance or improve efficacy.
It's worth noting that while naphthyridines have shown promise in preclinical studies, further research is needed to fully understand their safety and effectiveness in humans before they can be approved as therapeutic agents.
Bacterial drug resistance is a type of antimicrobial resistance that occurs when bacteria evolve the ability to survive and reproduce in the presence of drugs (such as antibiotics) that would normally kill them or inhibit their growth. This can happen due to various mechanisms, including genetic mutations or the acquisition of resistance genes from other bacteria.
As a result, bacterial infections may become more difficult to treat, requiring higher doses of medication, alternative drugs, or longer treatment courses. In some cases, drug-resistant infections can lead to serious health complications, increased healthcare costs, and higher mortality rates.
Examples of bacterial drug resistance include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and multidrug-resistant tuberculosis (MDR-TB). Preventing the spread of bacterial drug resistance is crucial for maintaining effective treatments for infectious diseases.
Azithromycin is a widely used antibiotic drug that belongs to the class of macrolides. It works by inhibiting bacterial protein synthesis, which leads to the death of susceptible bacteria. This medication is active against a broad range of gram-positive and gram-negative bacteria, atypical bacteria, and some parasites.
Azithromycin is commonly prescribed to treat various bacterial infections, such as:
1. Respiratory tract infections, including pneumonia, bronchitis, and sinusitis
2. Skin and soft tissue infections
3. Sexually transmitted diseases, like chlamydia
4. Otitis media (middle ear infection)
5. Traveler's diarrhea
The drug is available in various forms, including tablets, capsules, suspension, and intravenous solutions. The typical dosage for adults ranges from 250 mg to 500 mg per day, depending on the type and severity of the infection being treated.
Like other antibiotics, azithromycin should be used judiciously to prevent antibiotic resistance. It is essential to complete the full course of treatment as prescribed by a healthcare professional, even if symptoms improve before finishing the medication.
23S Ribosomal RNA (rRNA) is a type of rRNA that is a component of the large ribosomal subunit in both prokaryotic and eukaryotic cells. In prokaryotes, the large ribosomal subunit contains 50S, which consists of 23S rRNA, 5S rRNA, and around 33 proteins. The 23S rRNA plays a crucial role in the decoding of mRNA during protein synthesis and also participates in the formation of the peptidyl transferase center, where peptide bonds are formed between amino acids.
The 23S rRNA is a long RNA molecule that contains both coding and non-coding regions. It has a complex secondary structure, which includes several domains and subdomains, as well as numerous stem-loop structures. These structures are important for the proper functioning of the ribosome during protein synthesis.
In addition to its role in protein synthesis, 23S rRNA has been used as a target for antibiotics that inhibit bacterial growth. For example, certain antibiotics bind to specific regions of the 23S rRNA and interfere with the function of the ribosome, thereby preventing bacterial protein synthesis and growth. However, because eukaryotic cells do not have a 23S rRNA equivalent, these antibiotics are generally not toxic to human cells.
Streptococcus pneumoniae, also known as the pneumococcus, is a gram-positive, alpha-hemolytic bacterium frequently found in the upper respiratory tract of healthy individuals. It is a leading cause of community-acquired pneumonia and can also cause other infectious diseases such as otitis media (ear infection), sinusitis, meningitis, and bacteremia (bloodstream infection). The bacteria are encapsulated, and there are over 90 serotypes based on variations in the capsular polysaccharide. Some serotypes are more virulent or invasive than others, and the polysaccharide composition is crucial for vaccine development. S. pneumoniae infection can be treated with antibiotics, but the emergence of drug-resistant strains has become a significant global health concern.
Respiratory tract infections (RTIs) are infections that affect the respiratory system, which includes the nose, throat (pharynx), voice box (larynx), windpipe (trachea), bronchi, and lungs. These infections can be caused by viruses, bacteria, or, less commonly, fungi.
RTIs are classified into two categories based on their location: upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs). URTIs include infections of the nose, sinuses, throat, and larynx, such as the common cold, flu, laryngitis, and sinusitis. LRTIs involve the lower airways, including the bronchi and lungs, and can be more severe. Examples of LRTIs are pneumonia, bronchitis, and bronchiolitis.
Symptoms of RTIs depend on the location and cause of the infection but may include cough, congestion, runny nose, sore throat, difficulty breathing, wheezing, fever, fatigue, and chest pain. Treatment for RTIs varies depending on the severity and underlying cause of the infection. For viral infections, treatment typically involves supportive care to manage symptoms, while antibiotics may be prescribed for bacterial infections.
Microbial drug resistance is a significant medical issue that refers to the ability of microorganisms (such as bacteria, viruses, fungi, or parasites) to withstand or survive exposure to drugs or medications designed to kill them or limit their growth. This phenomenon has become a major global health concern, particularly in the context of bacterial infections, where it is also known as antibiotic resistance.
Drug resistance arises due to genetic changes in microorganisms that enable them to modify or bypass the effects of antimicrobial agents. These genetic alterations can be caused by mutations or the acquisition of resistance genes through horizontal gene transfer. The resistant microbes then replicate and multiply, forming populations that are increasingly difficult to eradicate with conventional treatments.
The consequences of drug-resistant infections include increased morbidity, mortality, healthcare costs, and the potential for widespread outbreaks. Factors contributing to the emergence and spread of microbial drug resistance include the overuse or misuse of antimicrobials, poor infection control practices, and inadequate surveillance systems.
To address this challenge, it is crucial to promote prudent antibiotic use, strengthen infection prevention and control measures, develop new antimicrobial agents, and invest in research to better understand the mechanisms underlying drug resistance.
Ribosomal RNA (rRNA) is a type of RNA molecule that is a key component of ribosomes, which are the cellular structures where protein synthesis occurs in cells. In ribosomes, rRNA plays a crucial role in the process of translation, where genetic information from messenger RNA (mRNA) is translated into proteins.
Ribosomal RNA is synthesized in the nucleus and then transported to the cytoplasm, where it assembles with ribosomal proteins to form ribosomes. Within the ribosome, rRNA provides a structural framework for the assembly of the ribosome and also plays an active role in catalyzing the formation of peptide bonds between amino acids during protein synthesis.
There are several different types of rRNA molecules, including 5S, 5.8S, 18S, and 28S rRNA, which vary in size and function. These rRNA molecules are highly conserved across different species, indicating their essential role in protein synthesis and cellular function.
Staphylococcus is a genus of Gram-positive, facultatively anaerobic bacteria that are commonly found on the skin and mucous membranes of humans and other animals. Many species of Staphylococcus can cause infections in humans, but the most notable is Staphylococcus aureus, which is responsible for a wide range of illnesses, from minor skin infections to life-threatening conditions such as pneumonia, endocarditis, and sepsis.
Staphylococcus species are non-motile, non-spore forming, and typically occur in grape-like clusters when viewed under a microscope. They can be coagulase-positive or coagulase-negative, with S. aureus being the most well-known coagulase-positive species. Coagulase is an enzyme that causes the clotting of plasma, and its presence is often used to differentiate S. aureus from other Staphylococcus species.
These bacteria are resistant to many commonly used antibiotics, including penicillin, due to the production of beta-lactamases. Methicillin-resistant Staphylococcus aureus (MRSA) is a particularly problematic strain that has developed resistance to multiple antibiotics and can cause severe, difficult-to-treat infections.
Proper hand hygiene, use of personal protective equipment, and environmental cleaning are crucial measures for preventing the spread of Staphylococcus in healthcare settings and the community.