5.+Therapies+(mg914)

=__**Therapies for Legionnaires Disease by Gina Murison (mg914):**__=

Legionnaires Disease (LD) was in the past (be more precise, when?) associated with a high level of mortality (50% of all hospitalised cases if treatment started late) but now due to earlier detection as well as a better understanding of the drugs needed to treat Legionnaires disease these rates have decreased good but ref? . Antimicrobials are used as an effective treatment for LD and are split into different groups – Macrolides, Quinolones, Tetracyclines and Rifampicin based on? . This aids the immune system in fighting off the bacteria and allows the patient to recover. Antimicrobials are given to the patient upon admittance intravenously. The choice of microbial agent is dependent on the efficacy and cost of the drug to be used as well as condition of the patient. This takes into account any other medical problems the patient may be suffering from such as being immunosuppressed or if the patient is pregnant. Treatment is also dependent on the severity of a suspected case of Legionnaires disease and in the most severe cases patients are treated with non-specific antimicrobials containing antimicrobials that are effective against LD whilst being tested for the strain. The patient is then switched to the more effective treatment upon diagnosis. Alongside the chosen treatment option, patients receive IV fluids to maintain hydration and in severe cases can also receive oxygen or assisted breathing. ref?

The most common antimicrobial treatment is Macrolides which inhibit protein synthesis at the 50S ribosomal complex and causes the growth of Legionnella pneumophilia to be inhibited through decreased translocation ( S evilla-sanchez //et al.//, 2010). Erythromycin was the first Macrolide produced and is commonly used as a first line treatment. This is due to its low dosage and effective efficacy. Although newer drugs such as Azithromycin and Clarithromycin have proven to be equally effective if not more effective than erythromycin but at lower doses (Zahar et al, 2008). As you can see in figure 1 (below) the low dosages of macrolides mean a lower toxicity to the body which is good treatment option during pregnancy and also in immunosuppressed patients. Good



Figure 1 – A table showing doses of drugs and route drug is given in patients suffering from legionnaires disease (Diederen. B.M.W, 2008).

Other treatment options include Tetracyclines which also target the 50S ribosomal complex and Quinolones which inhibit DNA synthesis which are observed in figure 2 (below). They are used to a great extent as a secondary treatment option in patients suffering from LD. Rifampicin targets RNA synthesis (figure 1) but due to the variation of efficacy its effectiveness has been questioned (Retsama et al, 2001). This variation has caused Rifampicin to not be used as a treatment option in the first instance but can be used as a last resort. Combined treatment alongside erythromycin was also looked into but showed that erythromycin alone had increased efficacy and so combined treatment using Rifampicin is also not recommended (Diederen. B.M.W, 2008). Good



Figure 2 – A table showing the mechanism of action for the main antibacterial classes (Retsama et al, 2001).

A new therapy that is being currently looked into are antimicrobial peptides (AMP’s) which are natural antibiotics that target the fatty acid composition of the phospholipid membrane. Warnericin RK is already showing promising results in the treatment of LD (Verdon et al, 2010). AMP’s will provide an alternative treatment option for LD and will allow a treatment to still be in place in the event of resistance to other antimicrobial drugs such as erythromycin. Very good, a table or graph with an o verview of the results would have been very good

=Conclusion:=

The patient 3 days previously complained of fever,malaise and respiratory problems. Amantadine was administered which is used in the treatment of influenza (Ison,M,2011). The patients symptoms progressively got worse and was administered to hospital with bilateral pneumonia. As legionella pneumophilia can present with flu-like symptoms this indicated that the patient was suffering from Legionella pneumophila. As the patient is also suffering from multi-system failure as a results of pnemonia he should be treated with antimicrobials intraveneously with assisted breathing or oxygen being used to help aid the patients recovery. As you don't want to risk resistance to the antimicrobials a cocktail of drugs may work better and give greater results for recovery. Antimicrobials will treat L.pneumophila quickly and efficiently and the patient should then make a full recovery.

=**__References:__**=
 * Daniel Sevilla-Sánchez, Dolors Soy-Muner and Néstor Soler-Porca, (2010), //Usefulness of Macrolides as Anti-inflammatories in Respiratory Disease//, Arch Bronconeumol. 46: 244-254.


 * Diederen. B.M.W, (2008), //Legionnella Spp and Legionnaires Disease//, Journal of infection, 56: 1- 12.


 * Ison,M, (2011), // Antivirals and Resistance: Influenza Virus, // Current opinion in Virology 1: 563-57


 * Julien Verdon, Jérome Labanowski, Tobias Sahr, Thierry Ferreira, Christian Lacombe, Carmen Buchrieser, Jean-Marc Berjeaud, Yann Héchard, (2011), //Fatty acid composition modulates sensitivity of Legionella pneumophila to warnericin RK, an antimicrobial peptide//, Biochimica et Biophysica Acta 1808: 1146–1153.


 * Retsema.J and Wenchi Fu, (2001), //Macrolides: structures and microbial target//, International Journal of Antimicrobial Agents, 18: 3–10.


 * Zahar. J.R and Kouatchet. A, (2008), //Legionnaires Disease: ‘Mise au point’//, Reamination,17: 206- 212.

Very good work, interesting and relevant facts have been reported and well discussed. In a couple of occasion you could have been more scientific (see comment at the very beginning. 2 mistakes in the use of the referencing protocol (in red)