This is a proposal describing a study to test the hypothesis that: The macrolide, erythromycin, normally used to treat individuals with community-acquired pneumonia, causes significant antibiotic resistance in patients in Europe but not individuals in the United States. 9 sources
To assess the prevalence of macrolide resistance (Erythromycin) among pneumococci in Europe and the United States and difference in frequency of Erythromycin use in both countries for respiratory infections. To identify the prevalent serotypes that cause pneumonia in both regions.
This will basically be a retrospective analysis of data collected by Public Health laboratories in Europe and institutions such as the Center for Disease Control in the United States. The two continents should be divided into 4 geographical regions each for the sake of clarity and convenience. Previous data relating to pneumococci isolated from patients with suspected pneumonia during a chosen specific period of time spanning about 5 years should be separated from the records. The serotype cultured in the various regions, sensitivity to Erythromycin, and frequency of Erythromycin prescription by doctors in these regions for ordinary respiratory infections should be assessed.
The prevalence of Erythromycin resistant pneumococci was higher in most areas of Europe as compared to the United States. The frequency of Erythromycin use in the U.S. For common respiratory infections was lower in the U.S.
The percentage of Erythromycin resistant pneumonia was significantly less in the surveyed regions of the U.S. As compared to Europe but nevertheless an increasing trend was observable. This might be directly related to the fact that Erythromycin use for common respiratory infections was more prevalent in Europe than in the U.S. But the practice was becoming popular in America as well.
The macrolide, erythromycin, normally used to treat individuals with community-acquired pneumonia, causes significant antibiotic resistance in patients in Europe but not individuals in the United States.
A reason for this is that Erythromycin is used more commonly and on a larger scale in Europe to treat ordinary respiratory infections as compared to North America.
Both these hypotheses can be tested by reviewing retrospectively data collected by Public Health Institutions in Europe and the United States. More specific data would of course require observational studies and thus the hypothesis would have to reduce or localize the geographic region it covers for accuracy and convenience.
Many studies have already been done all over Europe, especially Spain, Finland, and Turkey along with England and Denmark that are related to macrolide resistance, its causative factors and the pathogens involved.
These include research involved in the geno/phenotyping of the pneumococci that show macrolide resistance and delineation according to geographical region. Studies in the United States have been less detailed but due to an increasing awareness of the escalation of macrolide resistance in the United States over the past several years, scientists have begun to investigate the reasons in greater depth.
Materials and Methods
Due to the large geographical regions I have used in my hypothesis my study will be based on retrospective data already collected by recognized Public Health Institutions of the various regions.
I will analyze the invasive isolates spanning a 5-year period, collected by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance system in specific states, classified according to 4 geographical areas. Similar data will be assimilated from the 4 specified geographical regions of Europe.
Once I have gathered the data related to macrolide resistance in Europe and the United States over the past 5 years I will proceed to answer the following questions:
What are the various strains of pneumococci isolated that were resistant to Erythromycin?
Are their any detectable trends between resistant pathogen and region of isolation?
What are the minimum inhibitory concentrations (MICs) involved and is their a pattern?
What are the trends of macrolide use in the different regions?
Has there been a change in the frequency and type of use in medical practice in these various regions over the past 5 years?
Has there been a change in macrolide resistance over the past 5 years?
Tabulations and graphical representations can help present a clearer picture and comparison of the trends in Europe and the United States.
Due to the large scale of this study in terms of geographical area there is plenty of room for error due to insufficient or non-specific data. Most of the information to be gathered is from Institutions that have been studying disease trends in Europe and the United States. The data must cover a period of 5 years so as to show changing trends and give significance to any results. This however will again mean that the quantity of data is huge.
Data will be sufficient or not depending on the depth of research that has taken place in a given area. The strains of pneumococci may have been assessed according to phenotype and rarely in some centers in terms of their genetic structure. This data will however be relevant when compared to studies that have already occurred describing the genes that cause or enhance macrolide resistance.
Such information will help me hypothesize whether resistance to Erythromycin seen in Europe is due to specific types of pneumococci prevalent there or not. A 5-year study would show if there has been a change in the strains prevalent in the various geographical regions and whether this has made a difference to the macrolide resistance figures of that area. It will probably show that certain genotypes are associated with greater macrolide resistance and these will also show clonality of geographical trends.
A survey of the frequency of use of Erythromycin in the different regions will help me assess the cause of production of macrolide resistant strains of pneumococci and whether there may be an association between the two. Both outpatient prescriptions, production of Erythromycin in the regions, and its hospital use over the past 5 years, will assist in showing a connecting pattern. This data should show that in the areas where Erythromycin is used frequently, the tendency of having macrolide resistant pneumococci also increases. An increasing or decreasing trend of Erythromycin use over the 5 years in the various regions will support this hypothesis through a contrasting set of drug resistance data.
The success and accuracy of my study are dependent on the quality of available data. Much of this information will be less than specific to my study and I may have to make generalized assumptions reducing accuracy. Tabulation, graphs, and charts will help link associated data and clarify conclusions.
There has been an emergence of erythromycin resistance among pharyngeal isolates of group A streptococci and among middle ear isolates of Streptococcus pneumoniae in the United States. This showed a rising trend over the years and with increased frequency of macrolide use in the region. (Martin 2002, Mason 2003). Macrolide resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, is also increasing in the United States. From 1993 to 1999, macrolide use increased 13% while macrolide resistance increased from 10.6% in 1995 to 20.4% in 1999. (Hyde 2001)
In a study assessing the prevalence of antibiotic resistance and serotype distribution among pneumococci in England and Wales in 1990 and 1995 it was found that resistance to erythromycin increased from 2.8% to 8.6%.(Johnson 1996)
Two principal mechanisms of erythromycin resistance are known to exist among isolates of S. pneumoniae: a ribosomal methylase encoded by ermB, and an efflux pump encoded by mefA. Only 11 (2.8%) of the total of 394 erythromycin-resistant isolates did not fit one of these two profiles. (Gay 2000) Although M. phenotype isolates were previously thought to be the more benign because of low erythromycin MICs, studies show that the trend has turned toward increasingly higher erythromycin MICs often resistant to other antibiotic agents. (Hyde 2001) Investigators suggest the M. phenotype may become the dominant resistance mechanism "due to a combination of successful spread of clones within the pediatric population in the U.S. And selective pressure of macrolide use in this population." (Hyde 2001) While the M. phenotype is predominant in North America, several European countries report dominance of the MLSb phenotype. (Hyde 2001)
Canadian study shows that of 32 erythromycin-resistant isolates, 28 possessed the erm methylase gene (7 ermB and 21 ermTR/ermA) and 4 harbored the mefA gene; one isolate harbored both genes. The mreA gene was found in all the erythromycin-resistant strains as well as in 10 erythromycin-susceptible strains. The rate of erythromycin resistance increased from 5% in 1995-96 to 13% in 1998-99, which coincided with an increase in macrolide usage during that time. (de Azavedo 2001)
Resistance to erythromycin in group A streptococci has become an important problem among outpatients in Finland. (Seppala 1995) Logistic regression analysis showed that the proportion of isolates resistant to erythromycin clearly increased with increasing local erythromycin consumption by outpatients in 1991 (P =.006). (Seppala 1995)
Detection of erythromycin resistance genes by PCR indicated that, with the exception of one isolate with the CR phenotype, all M-phenotype isolates had the…