Group Analysis of Three Research Papers 10

Group Analysis of Three Research Papers 10

Research Methods – Bridget Torgerson and Rick Helgemo

Group Analysis of Three Research Papers

Bridget Torgerson and Rick Helgemo

Research Methods

May 1st, 2006

Humans have been battling with opportunistic infections, like Staphylococcus aureus, before they could even identify the bacteria. Colony morphology of S. aureus will show a unique golden hue after 48 hours incubation (37°C) and the species was named after an ancient gold coin minted in honor of Roman emperor Marcus Aurelius. Although most healthy people are not carriers of S. aureus, about a third of the population harbor the gram-positive cocci in their nasal (nares) cavity. Usually S. aureus is just fine “hanging out” in the asymptomatic human but when the right opportunity comes along (wound, sickness, surgery etc.) S. aureus makes its presence known.

One of the first lines of defense against S. aureus infection was the antibiotic penicillin. After S. aureus developed resistance to penicillin, and more was known about the bacteria, clinicians started prescribing methicillin (a.k.a. oxacillin). S. aureus has a special enzyme it produces called beta-lactamase. This enzyme can break open a beta-lactam ring, found on antibiotics in the penicillin family, and deactivate the function of the drug. Since the 1960’s, reports indicated S. aureus has now developed mechanisms to resist methicillin. Formerly, this methicillin resistant S. aureus (MRSA) was exclusively associated with health care settings and immunocompromised individuals. However, since the 1990’s, MRSA has become a big public health concern as otherwise healthy individuals are becoming infected from sources within the community.

We found three important papers that are good examples of current investigations on the impact MRSA has within the community, and how health facilities are dealing with this issue. Each paper was analyzed following a typical cyclical research process. We determined the potential problem, research question, goal of the study, and noted any potential subproblems, hypothesis, and data collected. Our interpretation of the data and opinion of the studies strengths and weaknesses follows the research analysis.

Articles Chosen (see proper reference at end):

1. Community – Associated Methicillin – Resistant Staphylococcus aureus Infection Among Healthy Newborns – Chicago and Los Angeles County, 2004, MMWR
2. A U.S. Population – Based Survey of Staphylococcus aureus Colonization, Annals of Internal Medicine
3. Contrasting Pediatric and Adult Methicillin – resistant Staphylococcus aureus Isolates, EID

Research Methods Used

Article #1:

Problem: An outbreak of methicillin resistant Staphylococcus aureus (MRSA) infection in healthy newborn babies at two independent hospitals in the United States.

Question: Can the use of the data obtained from investigations of these two unrelated hospitals give insight as to how the healthy infants contracted the bacteria and note any similar characteristics regarding the strain of MRSA?

Goal of the research: Identify the type of MRSA, Community – associated MRSA (CA-MRSA) or hospital – associated MRSA (HA-MRSA), and determine the pathogenicity and any possible hosts or reservoirs.

Potential Subproblem: If the MRSA was determined to not be the HA-MRSA strain, can it be determined that it is CA-MRSA and where in the community would a newborn infant contract such strains?

Hypothesis: Investigators compared the findings of these two hospitals to a similar case in 2002 at a New York City hospital. The New York City data concludes that the newborn cases were due to a community associated transmission. Using the Chicago and Los Angeles County data, the CDC wanted to support similar transmission in the new cases.

Data: Chicago hospital investigation found 11 cases of skin lesions where MRSA was isolated in the otherwise healthy newborn infants. The investigation identified no likely community sources (friends or family members with skin lesions) outside the hospital and the mothers of the infected newborns had no recent skin lesions. Nasal cultures from 135 health-care workers that had any potential contact with the newborn infants, diagnosed one nurse and one physician with nasal MRSA colonization. Comparing the pulsed – field gel electrophoresis (PFGE) and toxin gene identified, the two strains isolated from the health-care workers were indistinguishable from those isolated in the available infant cultures. Comparing the isolates from infant to infant also showed related characteristics to previously associated CA-MRSA outbreaks, with the exception of one infant isolate.

Los Angeles County also had 11 confirmed otherwise healthy newborn infant MRSA cases. Seven infant MRSA isolates available for further studies showed the same PFGE CA-MRSA outbreak strain markings. Health-care workers were not tested in this facility at the discretion of the Los Angeles County Department of Health Services.

The CDC determined that all three health departments (Chicago, LA County, and New York City) contained the MRSA strain, which has been associated with CA-MRSA outbreaks and sporadic infections in multiple states.

CA-MRSA has different genetic characteristics from HA-MRSA and develops different resistance mechanisms to specific antibiotics.

Interpretation: The two health-care worker cases in the Chicago hospital led the researchers to question whether the MRSA was spread from the nurse or physician to the infant or from the newly colonized infant to the health-care worker. Since the MRSA strain was proven to be similar to other documented cases of CA-MRSA in multiple states, it is less likely to be a transmission exclusively within the nursery. Also, there may have been more cases that have gone undiagnosed in patients where the infants received antibiotic therapy because of other unrelated illnesses or were able to recover without antibiotics or medical treatment.

Strengths/Weaknesses: Without the culturing of health-care workers at the LA County Hospital (and the previous New York City Hospital case) there was not sufficient evidence to correlate any possible connection between the tran

smission of MRSA from health-care worker to the newborn. Both facilities had small numbers of cases to obtain data but the specific data obtained from the PFGE was quite conclusive to compare each MRSA isolate. No cultures were collected from the mother’s of the positive infants and it would be interesting to see the number of MRSA isolates with obvious direct contact the mother/child relationship bestows. If such data were obtained, it should directly confirm a connection between transmission to any possible health-care workers that handled positive infants. The subproblem of “where the infants may have contacted CA-MRSA” was unanswered and community data was lacking.

Article #2:

Problem: Little is known about the epidemiology of the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and its colonization.

Question: What is the difference in risk factors, antibiotic resistance patterns, and genetic factors for colonization of methicillin sensitive Staphylococcus aureus (MSSA) and MRSA?

Goal of the research: Use the data obtained from the National Health and Nutrition Examination Survey (NHANES) to analyze U.S. risk factors that may contribute to the epidemiology of MRSA and compare to those risk factors associated with MSSA.

Potential Subproblem: Genetic factors may lead to further investigation of human genotyping and bacterial genotyping/serotyping. NHANES data is several years old but is the only national data available. Asymptomatic risk factors may differ from those infected with illness.

Hypothesis: Risk factors differ in those individuals infected with MSSA and MRSA.

Data: MSSA (culture obtained via nasal swab) sample prevalence was 31.6% verses MRSA prevalence of 0.84%. People 65 years or older, women, diabetics, and those hospitalized in long-term care facilities such as nursing homes were more likely to have a MRSA infection. Certain enterotoxins (A, and toxic shock syndrome toxin-1) were directly related to the MSSA strains verses MRSA enterotoxins (D, B and Panton-Valentine leukocidin). Antibiotic resistance mechanisms differ between strains and MRSA (all sensitive to trimethoprim-sulfamethoxazole and vancomycin) isolates can vary in specific antibiotic sensitivities.

Interpretation: There was a lot of data obtained in the study and many participants involved. The researchers conclude that the characteristics differ in those colonized with MSSA verses MRSA. Data was interpreted and explained using the statistical methods, programs, and displayed using tables.

Strengths/weaknesses: The large sample size was important for the success of this study. Previous data showing percentages of the U.S. population colonized with MRSA ranged from 20% - 60%. From the data obtained in this paper, the statistic has been narrowed to 31.6%. The authors carefully explained the risk factors and the limitations of data and possible reasons for certain specific risks. All statistics and statistical techniques were explained well and data presented clearly. However, with the NHANES data being four to five years old, modern epidemiological changes may not be reflected. Limitations and conclusions were discussed and further suggestions noted for follow-up research investigations.

Article #3

Problem: University of Chicago Hospitals performed studies on all inpatient and outpatient methicillin-resistant Staphylococcus aureus (MRSA) isolates to analyze differences in antibiotic resistance in adult verses pediatric cases and hospital- associated MRSA (HA-MRSA) verses community-associated MRSA (CA-MRSA).

Question: Does adult MRSA verses pediatric MRSA differ in antibiotic resistance and treatment protocols? Does the CA-MRSA require a different treatment protocol than the HA-MRSA infection?

Goal of the research: To determine what differences in antibiotic resistance exist (if any) and decide what alternative antibiotic has the most success in treating the adult and pediatric inpatient/outpatient hospital/community acquired cases.

Potential Subproblem: Certain antibiotics that have the most success in the adult may be contraindicated for treatment of a pediatric patient. Costs, availability, and administration of antibiotics must also be taken into account for potential hospital use. Defining the CA-MRSA cases and the HA-MRSA cases depends on the facility criteria and may require molecular testing.

Hypothesis: There is a difference in drug resistance between adult MRSA isolates verses pediatric MRSA isolates.

Data: 578 MRSA isolates were obtained from November 2003 to November 2004. These isolates were divided into four groups determined by patient age and CA-MRSA and HA-MRSA categories. Of the 578 patients, 201 were pediatric cases and 377 were from adults. Of the adult cases, 27.9% were collected on outpatients and pediatric cases collected 52.7% outpatient isolates. Most MRSA isolates from inpatients were CA-MRSA (adults 64.3% and pediatric 72.1%). Non- ß-lactam antimicrobial (erythromycin, clindamycin, ciprofloxacin, gentamicin, and tetracycline) resistance was significantly greater among the adult CA-MRSA isolates than the pediatric CA-MRSA isolates. However, the HA-MRSA isolates collected from adults and pediatric cases showed similar rates of the non-ß-lactam antimicrobial resistance.

Interpretation: Because the etiology of the CA-MRSA strains is still not well understood, in order to treat effectively, more conclusive data must be obtained to learn which strains non-ß-lactam antibiotics can treat. This data proves that there is a big difference in how a clinician should treat an adult case of CA-MRSA verses a pediatric case (besides dosage requirements). CA-MRSA infections seem to be on the rise since the mid 1990’s and can be quite distinct from the HA-MRSA isolates. University of Chicago Hospital system has defined criteria they follow to determine the CA-MRSA cases: temporal (isolate from a lesion < 72 hours after admission), host – risk – factor profile, antimicrobial drug susceptibility of the MRSA isolates, and certain molecular aspects of the isolates.

Strengths/weaknesses: This study was a good example of how an individual facility can participate in some “internal investigations” to gauge what their community is observing for CA-MRSA infections and what treatments are necessary. With the rise of the CA-MRSA cases, it is important to understand why they are different from HA-MRSA cases and how to treat individual patients depending on age. Each hospital has the “Formulary Committee” that decides what antibiotics they want to stock within their facility and what drugs they will prescribe to infected patients. Knowing the benefits and drawbacks of the specific antibiotics will aid in more aggressive treatment for adults and pediatric patients. There was a lot of information regarding how they conducted the study and some comparison to a couple other studies with interpretation of conflicting data. Also clearly explained are several limitations to the study in that the region was small and the sample may not be representative of the entire population and that several risk factors were not assessed that might aid in the interpretation of antibiotic resistance.

Conclusion: All three articles were well written and had supportive data. Each seemed easy to follow and provided good explanations for the individual methods and tools chosen. The first article did a great job of comparing current cases and using previous documented cases for correlation. Because of the large database, the MMWR reports are very well documented and strive to use their previous studies to provide support for the continued research endeavors. The Annals of Internal Medicine article contained a plethora of data based around survey statistics. The tables provided a clear visual display of the statistics and interpretation for the non-statistical reader to gain understanding and deeper clarity. The third article was a significant example of how a prospective study is useful, and necessary, in health facilities and can lead to better care for community members.
Reference:

Watson, J., Jones, R.C., Cortes, C., Gerber, S.I., et al. (2006). Community-Associated Methicillin-Resistant Staphylococcus aureus Infection Among Healthy Newborns – Chicago and Los Angeles County, 2004. Morbidity and Mortality Weekly Report, March 31, 2006 / Vol. 55 / No. 12. Retrieved from the Department of Health and Human Services, Centers for Disease Control and Prevention database.

Graham, P., Lin, S., Larson, E., (2006). A U.S. Population-Based Survey of Staphylococcus aureus Colonization. American College of Physicians, Annals of Internal Medicine, 144: 318-325.

David, M., Crawford, S., Boyle-Vavra, S., Hostetler, M., Kim, D., Daum, R., (2006). Contrasting Pediatric and Adult Methicillin-resistant Staphylococcus aureus Isolates. Emerging Infectious Diseases, Vol. 12, No. 4, April 2006, from www.cdc.gov/eid.