The delivery of aerosolized amikacin Amikacin Inhale; Nektar, CA, USA achieved high aminoglycoside amikacin concentrations in the fluid lining the epithelial surface of the lower respiratory tract, including in the pneumonic area of the lung, while maintaining safe serum concentrations.
No serious events were reported. Building on the results of this trial, a dose of mg every 12 h was chosen for the Phase III trial that is currently underway conducted by Bayer Healthcare and Nektar Therapeutics. In parallel, there is a paucity of data regarding the use of aerosolized colistin in patients without cystic fibrosis. Despite the lack of randomized controlled trials, the efficacy of inhaled colistin for MDR P.
Pereira et al. Fourteen of them had nosocomial pneumonia 11 had VAP and were concomitantly treated with intravenous polymyxin B. Interestingly, most of the patients selected for this study had previously failed intravenous polymyxin B therapy. A similar study of 60 critically ill patients infected with MDR Gram-negative bacteria received 2. No adverse effects related to inhaled colistin were recorded.
Recently, Falagas et al. In another meta-analysis of five randomized controlled trials of patients with nosocomial pneumonia including P.
Tobramycin was used in three studies, sisomycin in one and gentamicin in another. Concurrent systemic antibiotic was allowed to be used in four studies. Higher treatment success was observed in patients with nosocomial pneumonia who received treatment with antibiotics via the respiratory route inhaled or endotrachially instilled. However, neither the mortality rate nor the incidence of resistance was statistically different.
New formulations for inhaled therapy are currently under investigation for ciprofloxacin and aztreonam. An inhaled liposomal formulation of ciprofloxacin was recently approved by the US FDA for the management of bronchiectasis. Designed to prolong the short-acting nature of ciprofloxacin and to localize its activity to the lungs, the aerosolized formulation is intended to allow sufficient pulmonary exposure to treat these infections.
Similarly, an inhalable formulation of aztreonam lysinate has been tested in Phase III clinical trials in patients with cystic fibrosis who are colonized with pulmonary P. Preliminary data showed a significant reduction in P. Although the available data seem to suggest that aerosolized antimicrobial therapy for P.
Increasing resistance to antibiotics and the emergence of MDR strains have led to the development of experimental new antibacterial agents beside antibiotics. While antibiotics target bacterial growth, an attempt to attenuate the bacteria by intervening in the release of virulence factors is a promising alternative to combat the growing incidence of MDR bacteria. Many of these agents are antibodies that bind to proteins or receptors located in the bacterial body and therefore inactivate one of the virulence systems responsible for its pathogenesis.
While it is beyond the scope of this article to discuss all potential therapeutic targets, three monoclonal antibodies are undergoing clinical trials, with one of them being targeted for mechanically ventilated patients. In a mouse lung infection model, PcrV protein immunization provided protection against lethal lung infection, lung injury and cellular toxicity. Moreover, vaccination against PcrV increased the survival of challenged mice, and decreased lung inflammation and injury.
The antibody fragment, conjugated to polyethylene glycol PEG , is currently in clinical development for the treatment of P. The activity of the Fab fragment is considered key in reducing sensitivity to Pseudomonas proteases that degrade IgG antibodies, while PEGylation extends in vivo half-life and further reduces susceptibility to proteolytic inactivation. The ability of the Fab fragment to inactivate the TTSS results in the prevention of toxin injection into cells and averts the direct killing of macrophages by the TTSS that occurs even in the absence of toxins.
Management of this infection represents a difficult therapeutic challenge for critical care physicians, as the increasing resistance level of these microorganisms to most classes of antimicrobial agents frequently leads to clinical failure. Choosing adequate antibiotics is crucial to increase survival rate. The new generation of antibiotics does not appear to offer significant advantages over the traditional arsenal of antimicrobial agents.
For patients infected with MDR strains, very few clinical options exist. Colistin has emerged as a viable alternative for those infected with these strains. Whether combination therapy with colistin offers superior advantage over monotherapy requires future randomized trials. AES has received research grants from Pfizer and Wyeth pharmaceuticals.
AA: none to declare. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Approach to treatment of P.
Antipseudomonal therapy. New antipseudomonal antibiotics. Aerosolized antibiotics. Novel antibacterial agents. Transparency declarations. Update on the treatment of Pseudomonas aeruginosa pneumonia.
El Solh , Ali A. Oxford Academic. Ahmad Alhajhusain. Cite Cite Ali A. Select Format Select format. Permissions Icon Permissions. Abstract Pseudomonas aeruginosa is an important cause of nosocomial pneumonia associated with a high morbidity and mortality rate. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen.
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Many pharmacy students are introduced to antimicrobial spectrum of activity basics through microbiology coursework. During this time it is common for the student to receive a somewhat overwhelming amount of information and little guidance on the relative clinical importance of the material.
In my experience this is partly driven by non-clinician instructors being responsible for many university-level microbiology courses. As students move into higher-level classes, if they cannot adequately identify and define previously covered content, they are likely to find it difficult applying pharmacotherapy concepts to clinical cases. Not all students will struggle with this, but many do and simple study lists can be a great way to refresh or highlight some of the important points.
In an effort to provide an additional resource for learning antimicrobial spectrum basics, I have composed this article, which focuses on two of the most important pathogens in healthcare today: methicillin-resistant Staphylococcus aureus MRSA and Pseudomonas aeruginosa. MRSA is a catalase-positive Gram positive cocci and facultative anaerobe. In the U. Abstract Pseudomonas aeruginosa continues to cause serious infections, especially bacteremias, in hospitalized and immunocompromised patients.
Publication types Research Support, Non-U. Gov't Research Support, U.
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