Critical Appraisal S. aureus 

 

“New Treatments for Methicillin-resistant Staphylococcus aureus”

Author's note

Background on Staphylococcus aureus  

      In 1928, Alexander Fleming while working with the influenza virus accidently developed mold on a Staphylococcus aureus (S. aureus) culture plate with a bacteria free circle around it (Lectures, 1964). Mr. Fleming named the mold Penicillin. The drug was short lived. By 1945, resistance to the Penicillin developed which continues today (Dunbar, 2008).

      The resistance led to modifications of the bacteria and created antibiotics like Methicillin, introduced in 1961 (Dunbar, 2008). The 1990's saw a resurgence of S. aureus as a Nosocomial infection. Now in 2000's S. aureus is so strong a bacteria that individuals in the community have acquired the infection.

      Newer antibiotics are available now as Methicillin becomes outdated, just as penicillin in 1950. The new strain of resistance is 'Methicillin-resistant Staphylococcus aureus' (MRSA). Vancomycin the current gold standard treatment for S. aureus is losing strength. Pharmaceutical companies have and continue to modify the bacteria to combat the 'superbug.' These superbugs are virulent, and become stronger as antimicrobials lose the ability to combat the bacterium. Researchers work hard to manipulate antibiotics to rid the s. aureus infection by creating stronger antibiotics thus continuing a vicious cycle.

Authors of the article

      The authors of this peer review journal article from the Current Opinions in Critical Care, 2009 15:000-000,

       Martin E. Stryjewski, and G. Ralph Corey, both work for the Division of Infectious Diseases, Duke University Medical Center Durham, North Carolina, USA.  Stryjewski has received a research grant and is a consultant to Theravance Inc., and has provided consulting services to Astellas in the past. Corey is a consultant to Theravance Inc, Astellas, Merck Pfizer, Cerexa Cempra, Trius, Targanta GlaxoSmithKline, Arpida, Inimex, Cubist, and Novexel (Stryjewski, 2009). All of these companies produce pharmaceuticals. There seems to be a stake in at least one drug mentioned in the article relating to the company Theravance, Inc.

Purpose of the article

      The purpose of the review is new medications for Staphylococcus aureus. The MRSA pathogen is less susceptible to the once susceptible antimicrobial Vancomycin. “Rates of MRSA are increasing worldwide. In some centers MRSA is becoming less susceptible” (Stryjewski, 2009). The stated purpose of the article was to provide physicians with, “evidence based review” on newer antimicrobial medication (Stryjewski, 2009).

Introduction of the article

      The introduction clearly states the need for healthcare providers to understand the epidemiology of new MRSA antibiotics for proper use and application for treatment, “Delineate the role of new therapies in the treatment of infections due to MRSA” (Stryjewski, 2009).

Summary of the article

      The summary of the article reflects the new and experimental stages of medicine close to FDA approval. Each medication has advantages and disadvantages to the patient population, which in a table within the article elaborates.

Claims of the article

      The claims treatment of infectious disease relates to the, “recent findings Linezolid, Daptomycin, and Tigcycline in current use during the last decade to treat infections due to MRSA lupoglycopeptides (Telavancin, Dalbavancin, and Oritavancin) are in advanced phase of clinical development” (Stryjewski, 2009). “Similarly, new broad-spectrum cephalosporin's active against MRSA (e.g. Ceftobiporle and Ceftaroline) and a new dihydrofolate reducase inhibitor (Iclaprim) are in or have completed phase 3 studies” (Stryjewski, 2009).
 

Perspective of the article

      The article does provide information on new treatment, and treatment close to FDA approval for the use against MRSA. It is widely known that Vancomycin is not as effective as it once was in riding gram-positive antimicrobials. This article establishes strengths and weaknesses of these drugs. The article enables healthcare agents to identify the medication and the potential uses.

      The article establishes three constants regarding MRSA (Stryjewski, 2009). One, Vancomycin is not as effective, and increased in susceptibility, once thought of a Nosocomial infection is now out and in the community (Stryjewski, 2009). Two in "Latin America, Asia, Africa and Europe found that approximately 90% of S. Aureus strains isolated in ICUs are resistant to Methicillin "(Stryjewski, 2009). Third, resistances to Methicillin again in was found "in more than 60% of s. Aureus producing central line - associated blood stream infections in the ICUs from the United States" (Stryjewski, 2009).

      Supporting evidence in the article

      The scientific evidence the authors present supports the claims by identifying the break down resistance in terms of definitions. The study goes into detail not overall, but under each medication description utilizing a table (see appendix.).

      Researching information regarding the S. aureus article the following results are as follows. The Food and Drug Administration website confirms the status of the medications mentioned (http://www.fda.gov/). The results are consistent with the article.

      Reviewing material at the Center for Disease Control and Prevention (http://www.cdc.gov/) website two articles found incidentally, appear on the S. aureus reference list. The first article, “Staphylococcus aureus resistant to vancomycin: United States, 2002, MMWR Morbidity Mortality Weekly Report 2002; 51:565-567” (appendix 1). The next one, Centers for Disease Control and Prevention (CDC) article found is, “Reduced susceptibility of Staphylococcus aureus to vancomycin: Japan, 1996, MMWR Morbidity Mortality Weekly Rep 1997; 46:624-626” (appendix 2).

      A Medline search; A Service of the U. S. National Library of Medicine, and the National Institutes of Health (http://medlineplus.gov/) is a results of a search for Telavancin reference materials check confirms the use of the antimicrobials. The article, “A review of telavancin in the treatment of complicated skin and Structure of infections (cSSSI)” (appendix 3) supports what the authors state regarding the usage of Telavancin (Dunbar, 2008).

      The authors relied upon information from the studies, which the Food and Drug Administration false when investigating the drug Linezolid (Young, 2005). This creates a sense of falsehood for the article. The Linezolid incorrectly advertised information and as a result, the validity of the paper is suspect. The information cited in both the press release and the S. aureus article was identical.

      The comparisons between the antimicrobials listed with the advantages, and disadvantages of each medication for which patients should use the specific medication listed.

Layout and Formatting

      The poorly formatted layout within the article made the information hard to follow. The article discussed superiority of specific treatments and illnesses. The article lacks a forest plot. The goal of the paper was to introduce effective antimicrobials. Heterogeneity does exist within the subheadings, not as an overall effect. With the results stated within almost appears to sidetrack the reader from recognizing what is not included, formally identified meta-analysis. The text of the article mentions studies as a denotation within the reference list. This made it harder for the reader to have to stop and find the study mentioned within the article to review. While recognizing the article, as properly cited, it still made reading the information hard.  

Results

      The results of the article do show new antimicrobials that are effective against MRSA when Vancomycin is not the treatment of choice according to culture and sensitivity studies. Since MRSA invades physically in more than one place, it does not incorporate effectiveness with the antimicrobials versus Vancomycin with specificity. The article does comparisons between the antimicrobials.

Conclusion of the Article

      The results were presented that would have improved the article is statistical information represented in table form rather than presented within the text for ease of reading, along with titled representation of the studies with in the text. The table was interesting but did not correlate it with the comparison studies in the table. The authors appear to have a stake in the presentation of the findings because they either have a relationship with the one or more companies developing the pharmaceuticals, and with the one antimicrobial the Telavancin made by Theravance, Inc. Both authors are consultants, to the company. It was an evidenced based-review, without the opportunity for the reader to review the specific studies for inspection. Vancomycin once was the standard of treatment for staph infections. Now that the community acquired MRSA is out there with as a direct result of either overprescribing antimicrobials, or prescribing an ineffective pharmaceutical due to either lack of information, knowledge, or general education. The lack of Meta analysis prevents the reader from interpreting the results of the cited studies.  

Conclusion

      When does the cycle break? How do researchers find an antibiotic that S. aureus dies off? Researchers at this point and time have are working on identifying how to kill the bacteria, rather suppress it. Current studies have identified how the “golden pigment in S. aureus impairs neutrophil killing and promotes virulence through its antioxidant activity” (Liu, GY 2005.) There are researchers utilizing light (Zolfaghari, 2009). Therefore, it can only be a matter of time to eradicate this devastating and lethal bacterium. 
  

References 

Dunbar, L. T. (2008, February 4). A review of telvancin in the treatment of complicated skin and skin structure infections (cSSSI). Retrieved September 10, 2009, from PubMed.gov: Theraputic Clinical Risk Management; 4(1): 235-244: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2503659

Lectures, N. (1964). Physiology or Medicine 1942-1962, Sir Alexander Fleming-Biography. (Elsevier Publishing Company, Amsterdam,) Retrieved September 10, 2009, from Nobelprize.org: http://nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-bio.html

Liu GY, E. A. (2005, July 18). Staphylococcus aureus golden pigment impairs neutrophil killing promotes virulence through its antioxidant anctivity. Retrieved September 10, 2009, from BMC Microbiology PubMed.gov: http://www.ncbi.nlm.nih.gov/pubmed/16009720

Stryjewski, R. C. (2009). New treatments for methicillin-resistant staphylococcus aureus. Current Opinons in Critical Care 15:000-000 , p. 1-7. Apollo Library. http://swtuopproxy.museglobal.com/MuseSessionID=f5ac4a2724908798f52e50d3fc52d3bf/MuseHost=ovidsp.uk.ovid.com/MusePath/spb/ovidweb.cgi?&S=MJEOPDCLDPHFCFDDFNFLKHBGDPPKAA00&Complete+Reference=S.sh.35.36%7c6%7c1

Young, D. (2005, July 27). FDA warns Pfizer, Actelion about misleading information. Retrieved September 10, 2009, from American Society of Health-System Pharmacists: http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=1948

Zolfaghari, P. S. (2009, February 4). In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent. Retrieved September 10, 2009, from BioMed Central Microbiology: http://www.biomedcentral.com/1471-2180/9/27  

Appendix 

1. Staphylococcus aureus resistant to vancomycin: United States, 2002. MMWR Morbidity Mortality Weekly Report 2002; 51:565-567: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5126a1.htm

2. Reduced susceptibility of Staphylococcus aureus to vancomycin: Japan, 1996. MMWR Morbidity Mortality Weekly Rep 1997; 46:624-626: http://www.cdc.gov/ncidod/dhqp/pdf/ar/8_10.pdf

3. A review of telavancin in the treatment of complicated skin and Structure of infections (cSSSI): http://www.ncbi.nlm.nih.gov/pubmed/18728713?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum 

Items reviewed from the reference list:

13. Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med 2003; 348:1342-1347: http://content.nejm.org/cgi/content/full/348/14/1342

79. Advisory Committee Briefing Book; 2008: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4394b3-03-ARPIDA.pdf

70. FDA briefing document. Anti-infective Drug advisory Committee; 2008:

http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4394b2-03-FDA.pdf







 

 













































 

http://www.fda.gov/ohrms/dockets/ac/08/slides/2008-4394s2-03-Theravance.pdf 

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm101503.htm