Prevalance of Penicillin Resistant
Submitted By ameliamarcurius
1.1Background to the Problem
Streptococcus Pneumoniae is the causative agent of lung disease Pneumonia. Pneumonia was described as early as two thousand five hundred years ago by the Hippocrates. DR. Williams Osler, whom has studied pneumonia throughout his career, described pneumonia as the “captain of the men of death” owing to its great effect on humanity (Pneumonia,2006).The term pneumonia refers to any infection of the lung. Pneumococcal pneumonia is the term that is used to describe pneumonia that is caused by Streptococcus pneumoniae. Pneumococcal pneumonia not only affects the lungs but other parts of the body such as upper respiratory tract, middle ear, or the nervous system causing pneumococcal meningitis. Pneumococcal meningitis has a high fatality rate when compared to the other infections caused by Streptococcus pneumoniae. The means of transmission of Streptococcus pneumoniae is via respiratory droplet from the mouth or nose of an infected person or a carrier.
Penicillin became available in the 1940’s which changed radically the treatment of pneumococcal pneumonia which was based on watchful waiting. Despite this major development pneumonia still posed a major clinical problem today because of the resistance the organism developed against anti -microbial agents.Penicillin resistance is caused by a mosaic mutation of penicillin binding Protein (PBP) genes due to interspecies recombination of homologous genes. It is also recognized that a penicillin resistant pneumococcal in most cases is resistant to other antibiotics such as macrolide, tetracycline, co-trimoxazole, chloramphenicol and clindamycin.Antimicrobial resistance have limit the choice of treatment for many pneumonococcal diseased because of resistance these organism have built up against a number of antibiotice.For instance penicillin is said to be resistant to a list of drugs such fluoroquinolone,penicillin, macrolide,erythromycin etc.(Campbell &Silberman1998). Antimicrobial resistance in an economic stand point is very expensive in fact in the year 2000 US Department of Health and Human Services spent an estimate of US$1.7 billion on antibiotic production. What is taking place is that as soon as money is spent it to the development of new antibiotics against microorganism such as S.pneumoniae develope resistance over a period of time.Therefore more money will have to be pump in antimicrobial research.The largest expense of drug industry is the money spent on development of new antibiotics and, unfortunately, there is an absolute decline in the development of new antibiotics by pharmaceutical companies some of them have even halted antibiotics researches such as Aventis, Eli Lilly, Bristol-Myers Squibb and GlaxoSmithKline because of this ever growing resistance problem coupled with the fact antibiotics are of low price compared to other drugs such as neurological drug ,muscular-skeletal drug as well as short-course therapies.Currently pharmaceutical industry are the only industries that have been successfully developing antibiotics.This does not only threatens the development of new drugs against existing drug-resistant pathogens, but it also undermines the capacity to respond rapidly to the threat of emerging infectious diseases. (Bornova Izmir and Bornova Izmir,2008)..
2.2 The Problem
Pneumococcal disease is a matter of major concern in young children and the elderly in developing countries. It is estimated that pneumococcal disease is responsible for approximately 1.2 million deaths annually in children of South America. Currently in Guyana when compared to some of the other South American countries such as Peru and Colombia have a high incidence and mortality rate i.e. 2,000-3,000 cases/100,000 for children below the age of five in the year 2011.Research such as this will make the population aware of the level of antimicrobial resistance in streptococcus pneumoniae Guyana. So that certain preventative measures can be administered against the risk factors that are associated with antimicrobial resistance in streptococcus pneumoniae.
3.3Purpose of Research
The purpose of this study is mainly to gather data from some of the private and public laboratories in Guyana so as to ascertain the epidemiology of antimicrobial resistance S.pneumonia. This data will lead to the drawing of meaningful conclusions about the status of antimicrobial resistance in various sections of the population.
3.4Significance of Research
i. The findings from this research will give incite to the extent of antimicrobial resistance in Streptococcus pneumonia.
ii. Findings can lead to the formation of antibiotic resistance surveillance program which will collect data on antimicrobial resistance that can be use as the bases for the formation of preventative programs or policy which will reduce if not prevent future deaths that are associated with antibiotic resistance bacteria.
iii. Information about resistance in Streptococcus pneumoniae will be important in defining prognosis for infected patients.
The date for this study is obtained strictly from various hospital log book in Guyana over a period of five years .However this study relies solely on the availability of these hospital records. Efforts were made by the researcher to minimize this by introducing a time frame of five years.
i. What is the prevalence of Penicillin resistance S.pneumoniae in the Guyanese population? ii. What is the pattern of prevalence as it relates to the increase in age? iii. What is the prevalence of Penicillin resistance Gram positive Cocci in the Male and Female population of Guyana?
iv. Prevalence of penicillin resistant Streptococcus pneumoniae in both invasive and non-invasive Streptococcus pneumoniae?
3.7Definition of Terms
I. Antimicrobial agents- Are compounds that inhibit or slows down the growth of microbes
II. Multidrug-resistant--Is use to describe microorganism that are resistant a more than one antimicrobial agents.
III. Net present value - Parameter by which Drug companies choose areas of investment
IV. Non-susceptible strains- Strains with diminished susceptibility.
V. Pneumonia-The term pneumonia refers to any infection of the lung.
VI. Pneumococcal disease- Pneumococcal diseases are diseases caused by Streptococcus pneumoniae.
VII. Penicillin resistant–Is use to describe microorganism that can grow in the presence of antibiotic penicillin.
VIII. Penicillin susceptibility –Is the term used to describe microorganism that cannot grow in the presence of antibiotic penicillin.
IX. Prevalence-Is the number of existing cases.
X. Populations- A particular section, group, or type of people or animals living in an particular.
XI. Strains-A strain is a genetic variant of a micro-organism.
XII. Susceptible strains –Strains when exposed to a particular antibiotic will lead to the death or weakening of the bacteria.
2.0 Literature Review
“The emergence and spread of microbial resistance is a true global threat, affecting both industrialized and non-industrialized countries. Overuse of antibiotics in industrialized countries has contributed to an acceleration of the problem, as has underuse of efficacious antimicrobial drugs in developing countries as a result of poverty and the consequent lack of effective health care (WHO, 2000).” A retrospective study conducted in Uruguay and Argentina using information from a hospital-based surveillance system in hospitalized children less than five years of age who have had S .pneumoniae between June 1993 and October 1996.This study assess the differences in risk factors between children infected with penicillin-sensitive and drug-resistant Streptococcus pneumoniae .Three hundred and eighty children were eligible for this study of which two hundred and seventy four records were available .It was found that Ninety-nine of them had drug resistant Streptococcus pneumoniae, forty-six had intermediate susceptibility (minimum inhibitory concentration, 0.12–1.0 μg/mL) and fifty three showed high-level resistance. This study reveals that most of the children were affected by drug resistant Streptococcus pneumoniae and that previous penicillin use,private medical coverage ,are all risk factors associated for having drug resistant streptococcus pneumoniae. (Shelley et al.,1999).
In a study conducted in Middle Tennessee between the period 1990 and 1999 that focuses on the Antimicrobial susceptibility of streptococcus pneumoniae.It was found that there was a significant increase in the percentage of non-penicillin-susceptability. Before the year 1997, 10% of isolates were resistant to penicillin which later increase progressively to 26% in 1997, 56% in 1998, and 70% in 1999. ( Agata et al., 2001).In an ANSORP Study done in eleven Asian countries between the period 1996-1997 , it was found that penicillin resistance has greatly increased among isolates from countries such as Vietnam, China, Sri Lanka, and Malaysia, Korea, Taiwan, and Thailand, Vietnam, Hong Kong, Korea, and Taiwan. A continuation of this study was done in January 2000 to June 2001.Majority of the isolates were not susceptible to penicillin, 23% were intermediate susceptible , and 29.4% were penicillin resistant (MICs ≥ 2 mg/liter).The highest of prevalence in terms of countries was seen in Vietnam followed by isolates from Korea, Hong Kong and Taiwan. These two Asian studies show that Asian countries have serious issues as it relates to penicillin resistance. (Pai et al., 1999).In a study conducted in the united states that compares resistance rate of Streptococcus pneumoniae during the period 1994–1995 to 1997–1998 and1999-2000 .The 1997–1998 study use twenty four of the medical centre that was used in 1994–1995 study. This study showed an overall increase in penicillin resistance within that time. The 1999-2000 study that include thirty three of the thirty four centers participating in the 1997–1998 study showed an continued increase in trend in penicillin resistance in Streptococcus pneumoniae despite the introduction of preventative program me. ( Brueggemann et al.,2001). In Atlanta the annual incidence of invasive pneumococcal infection was rated as thirty cases per one hundred thousand populations.
In a laboratory base surveillance study conducted for drug resistance S. pneumoniae among patients with invasive pneumococcal infections in Atlanta between January to October 1994.
Antimicrobial resistance was found to be in both children and adult .However it is more prevalent in children less than six years old. Whites were more likely to have invasive S.pneumoniae infection cause by antimicrobial resistance than blacks. In fact forty one percent of the S. pneumoniae isolates from white children was found to be resistant to penicillin. (Breiman et al., 1995).In another American study conducted with the use of data from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention on Patient with invasive pneumococcal disease between the periods 1995 to 1998. In this analysis high level of resistance as well as intermediate resistance were defined as “resistance” According to the National Committee for Clinical Laboratory Standards. Out of three thousand and seventy five isolates 24% of them were penicillin resistant. The Highest rate of resistant was fund in states such as Georgia (33 percent) and Tennessee (35 percent) as well as in children under the age of five (32%) when compared to children five years and above (21%).Like the study conducted by (Breiman et al., 1995) which shows that whites were more likely than blacks to have penicillin resistant the same was found in this study It was also found that penicillin resistant isolates were more likely to be resistant to other antimicrobial agents than penicillin susceptible isolates. (Schuchat et al.,2000).
Prevalence of Macrolide resistance in S.pneumoniae
[i] “Macrolide are generally regarded as the main alternative to β-lactam treatment of respiratory trac infection S.pneumoniae. Data from the Alaxander project,however, indicate that macrolide resistance in S.pneumoniae is increasing. In some regions,the prevalence of erythromycin-resistant S.pneumoniae is two to five times higher than that of penicillin –resistant strains”(Marchese,A.,2000).
In 1997 in hong Kong majority of S.pneumoniae was found to be resistant to macrolides. Studies done in France, Belgium and Italy have all shown a growing increase in macrolides resistance (Flamingham et al., 2000).
There is high prevalence of drug resistant Streptococcus pneumonia in Guyana.
4.1Description of the Subject
This study solely depends on records obtained from Laboratory log books across Guyana. Record will be obtained from patients who are diagnosed with infections caused by streptococcus pneumoniae within the last five years. The selection of the sample will be done non-randomly with the use of the convenience sampling method. The convenience sampling method is employed to cater for cases where laboratory might be unable give the data because of various reasons such of loss of data due to improper record keeping practice or cases where laboratory are out of reach of the researcher. An estimate of over Six Hospital laboratories will be used to retrieve information for this research.
4.2 Study Design
Obtaining records from all the laboratories in Guyana will a privilege. However it is not necessary when you can use a sample. Black and Champion (1976), [ii]“Define a sample as a portion of elements taken from a population, which is considered to be representative of the population”. The research design use will be retrospective study design (survey) in which records will be obtained from various public and private Laboratories across Guyana The data on independent and dependant variables will be obtained after the submission of a request from the supervisor of Research to the respective Laboratories.
In this research the independent variable is drug resistance Streptococcus pneumonia while the Dependent variable is High Prevalence. The independent variable is qualitative and the dependent variable is quantitative.
4.4 Method of measuring each Variable
Both variables will be measured with the use of records obtained from the respective Laboratories Log book.
5.0 Ethical Considerations
Permission will have to be sought from the Ethical Review Committee (ERC) of the Ministry of Health to continue this project. Permission will have to be obtained from various laboratories head before the records can access.
6.0 Data Analysis
In this research the data that will be collected from the laboratories will be entered in MS EXCEL for analysis. SPSS Version would be used to analyze statistical data obtained using suitable statistical measures. The t-test, Chi-square or the Correlation are the test that will be included.
7.0 Budget Considerations
|ITEMS |UNIT |QUATITY |COST |
|Research Proposal |Booklet |One (1) |$260 |
|Materials and Supplies |Paper |one (1) realms |G$2000 |
| |Pens |Three(3) |G$500 |
| |Pencils |Three(3) |G$200 |
| |File folders (cardboard) |Three (3) |G$2000 |
| |Clipboard holders | | |
| | |Two (2) |G$300 |
| | | | |
| | | | |
|Transportation |Public transportation |Ten trips |G$6000 |
|Total | | |G$11,260 |
8.0 Time Schedule
| |Activity |Deadline Date |
|1 |Communicate with Research supervisor |January 12th 2012 |
|2 |Decide on research topic |January 17th 2012 |
|3 |Obtain permission from Private/Public Lab |12th March 2012 |
|4 |Put measures in place to obtain Data from labs. |15th march 2012 |
|5 |Obtain necessary Data from labs. |19th March 2012 |
|6 |Consult with statistician to ensure information being entered and analyzed |22nd March 2012 |
| |correctly | |
|7 |Write Chapter on presentation and analysis of data |29th March 2012 |
|8 |Write summary of findings/abstract, Conclusions, Recommendations etc. |5th April 2012 |
|9 |Write final draft, include acknowledgment etc. |15th April 2012 |
|10 |Edit report submit | |
|11 |Oral presentation | |
Arnold, K. E., Leggiadro, R. J., Breiman, R. F., Lipman, H. B., Schwartz, B., Appleton, M.A.,… Facklam RR.(1996). Risk factors for carriage of drug-resistant Streptococcus pneumoniae among children in Memphis, Tennessee. Journal of Pediatrics, 126(6),75764. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8648533
Baquero, F. (1996). Trends in antibiotic resistance of respiratory pathogens: an analysis and commentary on a collaborative surveillance study. Journal of Antimicrobial Chemotherapy 38, Suppl. A, 117–32. Retrieved from http://jac.oxfordjournals.org/content/38/suppl_A/117.abstract
Oguz ,Resat Sipahi.,Bornova Izmir.(2008).Economics of Antibiotic Resistance: Effects of Antibiotic Resistance on Industrial Antibiotic R&DRetrived from http://www.medscape.com/viewarticle/580479_14 2008;6(4):523-539
Centers for Disease Control and Prevention Web site. Pneumonia. Available at: http://www.cdc.gov/nchs/FASTATS/pneumonia.htm. Accessed on Jan. 19 2011
Clavo-Sanchez, A. J., Girón-González, J. A., López-Prieto, D., Canueto-Quintero, J., Sánchez-Porto, A.,… Vergara-Campos, A. (1997). Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: a multicenter sutdy. Clinical Infectious Diseases, 24(6),1052– 9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9195057
Cynthia G. Whitney.,Monica M. Farley., James Hadler., Lee H. Harrison., Catherine Lexau., Arthur Reingold.,… Schuchat.(2000). Increasing Prevalence of Multidrug-Resistant Streptococcus pneumoniae in the United States. The New England Journal of Medicine,343(26),1917-1924.Retrived from http://www.ncbi.nlm.nih.gov/pubmed/11136262
Felmingham,D., Gruneberg,N.& the Alexander Project Group.(2000).The Alexander Project 1996-1997:latest suscepability data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections.Journal of Antimicrobial Chemotherapy 45,191-203.
Goldstein, F. W. & Garau, J. (1997). 30 years of penicillin-resistant S. pneumoniae: myth or reality. Lancet, 350, 233–4. Retrieved from http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2805%2962222-2/fulltext
Gary V. Doern.,Kristopher P. Heilmann.,Holly K. Huynh.,Paul R. Rhomberg.,Stacy L. Coffman.,Angela B., Brueggemann.(2001).Antimicrobial Resistance among Clinical
Isolates of Streptococcus pneumoniae in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995.American Society for Microbiology Antimicrobial Agent and Chemotherapy ,45(6),1721-1729. Retrieved from http://aac.asm.org/content/45/6/1721.full
G. Douglas Campbell, Jr., Ronald Silberman.(1998).Drug-Resistant Streptococcus pneumoniae. Clinical Infectious Diseases, 26,1188–95. Retrieved from http://cid.oxfordjournals.org/content/26/5/1188.full.pdf
Jae-Hoon Song., Nam Yong Lee., Satoshi Ichiyama., Ryoji Yoshida., Yoichi Hirakata., Wang Fu.,… Atef Shibl1.(2004). High Prevalence of Antimicrobial Resistance among Clinical Streptococcus pneumoniae Isolates in Asia (an ANSORP Study).American Society for Microbiology.48(6), 2101-2107. http://aac.asm.org/content/48/6/2101.full
Jo Hofmann., Martin S. Cetron.,Monica M. Farley.,Wendy S. Baughman., Richard R. Facklam., John A. Elliott.,… Robert F. Breiman.(1995).The Prevalence of Drug-Resistant Streptococcus pneumoniae In Atlanta. The New England Journal of Medicine.333, 481-486.Retrieved from http://www.nejm.org/doi/full/10.1056/NEJM199508243330803
Medline Plus Web site. Pneumonia. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000145.htm. Accessed Feb. 13 2012
Nava, J. M., Bella, F., Garau, J., Lite, J.,Morera, M.-A., Martí, C. et al. (1994). Predictive factors for invasive disease due to penicillin-resistant Streptococcus pneumoniae: a population-based study. Clinical Infectious Diseases ,19(5), 884–90. Retrieved from http://cid.oxfordjournals.org/content/19/5/884.abstract
Pradier, C., Dunais, B., Carsenti-Etesse, H. & Dellamonica, P. (1997). Pneumococcal resistance patterns in Europe. European Journal of Clinical Microbiology and Infectious Diseases, 16(9), 644–7. Retrieved from http://www.springerlink.com/content/n304nt373t0nm1tr/
11Schito,G C.,Debbia,E. A.,marchese,A.(2000).The evolving threat of antibiotic resistance in Europe:new world data from the Alexander Project.Journal of Animicrobial Chemotherapy 46,Suppl.T1,3-9
Wolfgang Witte.(1999).Antibiotic resistance in gram-positive bacteria: epidemiological aspects. Journal of Antimicrobial Chemotherapy, 44, 1-9.Retreaved from http://jac.oxfordjournals.org/content/44/suppl_1/1.full.pdf
[iii] World Health Organization.(2000).Overcoming Antimicrobial Resistance.World Health Report on Infectious Diseases.World Health Organization,Geneva.
Yi-Wei Tang.,Haijing Li.,Jane P. Griffin., David W. Haas.,Erika M. C. D'Agata.( 2002).
Rapidly Increasing Prevalence of Penicillin-Resistant Streptococcus pneumoniae in Middle Tennessee: a 10-Year Clinical and Molecular .Analysis.Journal of Clinical Microbiology,40(2),395–399. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC153403/