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Surgical Infections 2006Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection among patients receiving mechanical ventilation. Failure to... (Review)
Review
BACKGROUND
Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection among patients receiving mechanical ventilation. Failure to initiate appropriate and adequate therapy (i.e., the etiologic organism is sensitive to the therapeutic agent, the dose is optimal, and the route of administration is correct) promptly in patients with VAP has been associated consistently with higher mortality rates. However, effective antimicrobial therapy for patients with true VAP can be achieved while avoiding excessive antibiotic use and the emergence of multidrug-resistant strains in the ICU.
METHOD
Review of the pertinent English-language literature.
RESULTS
Antimicrobial therapy for patients with VAP should follow a two-stage process. The first stage is identifying true pneumonia rapidly and starting therapy with an empirical regimen that is likely to be appropriate. In general, this requires using broad-spectrum antibiotics in all patients in whom there is a possibility that the etiologic pathogen could be difficult to treat (e.g., multi-drug-resistant pathogen). The second stage focuses on trying to achieve this objective without overusing and abusing antibiotics and combines a number of steps, such as stopping therapy in patients with a low probability of the disease, streamlining treatment once the etiologic agent is known, switching to monotherapy after three to five days, and shortening the duration of therapy to seven or eight days, as dictated by the patient's clinical response to therapy and information about the bacteriology of the infection.
CONCLUSION
Although such a strategy seems a logical way to manage patients with VAP, data are still needed to determine how best to achieve this process.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Ventilators, Mechanical
PubMed: 16895514
DOI: 10.1089/sur.2006.7.s2-81 -
International Journal of Antimicrobial... 2001The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation'... (Review)
Review
The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts.
Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Design; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Tissue Distribution
PubMed: 11574189
DOI: 10.1016/s0924-8579(01)00410-1 -
International Journal of Clinical... 2022Intestinal microbiota plays a key role in regulating the pathogenesis of human disease and maintaining health. Many diseases, mainly induced by bacteria, are on the rise... (Review)
Review
Intestinal microbiota plays a key role in regulating the pathogenesis of human disease and maintaining health. Many diseases, mainly induced by bacteria, are on the rise due to the emergence of antibiotic-resistant strains. Intestinal microorganisms include organisms such as bacteria, viruses, and fungi. They play an important role in maintaining human health. Among these microorganisms, phages are the main members of intestinal viromes. In particular, the viral fraction, composed essentially of phages, affects homeostasis by exerting selective pressure on bacterial communities living in the intestinal tract. In recent years, with the widespread use and even abuse of antibacterial drugs, more and more drug-resistant bacteria have been found, and they show a trend of high drug resistance and multidrug resistance. Therefore, it has also become increasingly difficult to treat serious bacterial infections. Phages, a natural antibacterial agent with strong specificity and rapid proliferation, have come back to the field of vision of clinicians and scholars. In this study, the current state of research on intestinal phages was discussed, with an exploration of the impact of phage therapy against infectious diseases, as well as potential application beyond infectious diseases.
Topics: Humans; Phage Therapy; Bacterial Infections; Bacteriophages; Bacteria; Anti-Bacterial Agents; Communicable Diseases
PubMed: 36263241
DOI: 10.1155/2022/4913146 -
Drugs Apr 1996Erythromycin and other macrolides have enjoyed a renaissance in the 1970s, 1980s and 1990s secondary to the discovery of "new' pathogens such as Chlamydia, Legionella,... (Review)
Review
Erythromycin and other macrolides have enjoyed a renaissance in the 1970s, 1980s and 1990s secondary to the discovery of "new' pathogens such as Chlamydia, Legionella, Campylobacter and Mycoplasma spp. Erythromycin is an important therapeutic agent in the paediatric age group for several reasons: (a) it exhibits proven efficacy for a wide range of infections (upper and lower respiratory tract infections, skin/skin structure infections, prophylaxis of endocarditis/acute rheumatic fever/ophthalmia neonatorum and pre-colonic surgery, campylobacteriosis, chlamydial and ureaplasmal infections, diphtheria, whooping cough, streptococcal pharyngitis) and gastrointestinal (GI) dysmotility states; (b) intravenous formulations are widely available; and (c) it is available in a number of formulations as a generic product, which is likely to result in significant cost savings. Nevertheless, erythromycin and similar earlier macrolides are characterised by a number of drawbacks including a narrow spectrum of antimicrobial activity, unfavourable pharmacokinetic properties and poor GI tolerability. Newer macrolides such as clarithromycin and azithromycin are useful in serving the needs of paediatric patients who are erythromycin-intolerant or who have infections caused by organisms that are intrinsically erythromycin-resistant, or for which a high percentage of strains are resistant (e.g. Haemophilus influenzae, Helicobacter pylori, Mycobacterium avium complex). In addition, these newer macrolides may be considered as alternatives to oral amoxicillin-clavulanic acid, second or third generation cephalosporins, or erythromycin plus sulphonamide in this patient population. Selection between specific macrolides and between macrolides and other antibiotics in the paediatric population is likely to depend, at least for the immediate future, on separate comparisons of product availability, cost, effectiveness and tolerability profiles.
Topics: Anti-Bacterial Agents; Biological Availability; Child; Child, Preschool; Communicable Diseases; Cost-Benefit Analysis; Drug Interactions; Drug Resistance, Microbial; Humans; Infant; Injections, Intravenous; Macrolides; Pediatrics
PubMed: 8706592
DOI: 10.2165/00003495-199651040-00002 -
Journal of the South African Veterinary... Sep 2000Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful... (Review)
Review
Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.
Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; Cattle; Female; Mammary Glands, Animal; Mastitis, Bovine; Primary Prevention; Treatment Failure
PubMed: 11205172
DOI: 10.4102/jsava.v71i3.714 -
Current Topics in Medicinal Chemistry 2016The essence of successful antimicrobial chemotherapy lies in selective toxicity of the agent towards the pathogen. An ideal antimicrobial agent should kill pathogens... (Review)
Review
The essence of successful antimicrobial chemotherapy lies in selective toxicity of the agent towards the pathogen. An ideal antimicrobial agent should kill pathogens effectively with little or no effect on host cells. There is a dearth of antibiotic and antimicrobial therapies due the rapid development of microbial resistance to these agents, as evidenced by increasing incidences of hospital acquired infections. This challenge necessitates the discovery and development of novel and effective antimicrobial agents. One promising approach is Antimicrobial Peptides (AMPs), which are synthesized by a large number of organisms. The presence of AMPs throughout evolution hints at their importance. The first and foremost interaction between AMPs and target cell occurs at the membrane of the pathogen. The details about these interactions will pave way for the development of new synthetic analogues or modified analogues of existing AMPs. Mechanistic insights into adoption of different structures in presence of bacterial membranes (and with their specific targets) will enhance our understanding and knowledge about these agents and their detailed mechanism of action. AMPs interact with lipids and form lipid-AMP complexes that create AMP-lined ion channels, which in turn modulate the membrane potential. This may have an effect on various biological processes leading to arrest of cell growth or cell death. This review summarizes the ion channel formation property of AMPs as an effective approach in dealing with neutralization of pathogenic microbes.
Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteria; Microbial Sensitivity Tests
PubMed: 26139119
DOI: 10.2174/1568026615666150703115454 -
Biointerphases Aug 2018The ability to control the properties of bio-inspired liquid-infused surfaces is of interest in a wide range of applications. Liquid layers created using oil-infused...
The ability to control the properties of bio-inspired liquid-infused surfaces is of interest in a wide range of applications. Liquid layers created using oil-infused polydimethylsiloxane elastomers offer a potentially simple way of accomplishing this goal through the adjustment of parameters such as curing agent ratio and oil viscosity. In this work, the effect of tuning these compositional parameters on the properties of the infused polymer are investigated, including infusion dynamics, stiffness, longevity in the face of continuous liquid overlayer removal, and resistance to bacterial adhesion. It is found that that curing agent concentration appears to have the greatest impact on the functionality of the system, with a lower base-to-curing agent ratio resulting in both increased longevity and improved resistance to adhesion by Escherichia coli. A demonstration of how these findings may be implemented to introduce patterned wettability to the surface of the infused polymers is presented by controlling the spatial arrangement of bacteria. These results demonstrate a new degree of control over immobilized liquid layers and will facilitate their use in future applications.
Topics: Anti-Bacterial Agents; Bacterial Adhesion; Chemical Phenomena; Dimethylpolysiloxanes; Escherichia coli; Surface Properties
PubMed: 30092645
DOI: 10.1116/1.5039514 -
New Biotechnology Dec 2015Bacillus subtilis has the capacity to produce more than two dozen bioactive compounds with an amazing variety of chemical structures. Among them, bacilysin is a... (Review)
Review
Bacillus subtilis has the capacity to produce more than two dozen bioactive compounds with an amazing variety of chemical structures. Among them, bacilysin is a non-ribosomally synthesized dipeptide antibiotic consisting of l-alanine residue at the N terminus and a non-proteinogenic amino acid, l-anticapsin, at the C terminus. In spite of its simple structure, it is active against a wide range of bacteria and fungi. As a potent antimicrobial agent, we briefly review the biochemistry and genetics as well as the regulation of bacilysin biosynthesis within the frame of peptide pheromones-based control of secondary activities. Biological functions of bacilysin in the producer B. subtilis beyond its antimicrobial activity as well as potential biotechnological use of the biosynthetic enzyme l-amino acid ligase (Lal) are also discussed.
Topics: Anti-Bacterial Agents; Bacillus subtilis; Dipeptides; Gene Expression Regulation, Bacterial; Models, Biological
PubMed: 25644640
DOI: 10.1016/j.nbt.2015.01.006 -
Journal of the Royal Society, Interface Apr 2024Biofilms are responsible for most chronic infections and are highly resistant to antibiotic treatments. Previous studies have demonstrated that periodic dosing of...
Biofilms are responsible for most chronic infections and are highly resistant to antibiotic treatments. Previous studies have demonstrated that periodic dosing of antibiotics can help sensitize persistent subpopulations and reduce the overall dosage required for treatment. Because the dynamics and mechanisms of biofilm growth and the formation of persister cells are diverse and are affected by environmental conditions, it remains a challenge to design optimal periodic dosing regimens. Here, we develop a computational agent-based model to streamline this process and determine key parameters for effective treatment. We used our model to test a broad range of persistence switching dynamics and found that if periodic antibiotic dosing was tuned to biofilm dynamics, the dose required for effective treatment could be reduced by nearly 77%. The biofilm architecture and its response to antibiotics were found to depend on the dynamics of persister cells. Despite some differences in the response of biofilm governed by different persister switching rates, we found that a general optimized periodic treatment was still effective in significantly reducing the required antibiotic dose. As persistence becomes better quantified and understood, our model has the potential to act as a foundation for more effective strategies to target bacterial infections.
Topics: Humans; Bacteria; Bacterial Infections; Anti-Bacterial Agents; Biofilms
PubMed: 38593842
DOI: 10.1098/rsif.2024.0078 -
International Journal of Antimicrobial... Mar 2014The judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise... (Review)
Review
The judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise toxicity. Critical to dose optimisation is an understanding of the pharmacokinetics and pharmacodynamics of available drugs. Optimal dosing strategies may take advantage of pharmacokinetic/pharmacodynamic (PK/PD) principles so that antibiotic dosing can be individualised to assure effective bacterial killing in patients who have altered pharmacokinetics or who have infections with less susceptible or resistant organisms. This review will outline the fundamentals of antimicrobial pharmacokinetics/pharmacodynamics through discussion of antibacterial agents most often used in children. We aim to highlight the importance of dose optimisation in paediatrics and describe non-conventional dosing strategies that can take advantage of PK/PD principles at the bedside.
Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Humans
PubMed: 24389079
DOI: 10.1016/j.ijantimicag.2013.11.006