1. MRSA: The Re-hospitalizationof Those at Risk
Epidemiology 5300- Group 8
Shivani Arora
Cymphoni Campbell
Ikponmwosa Enofe
Elizabeth Garciri
Chiao-Chin Lin
Karan Shah

2. Introduction
Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of Staphylococcus aureus
bacteria, resistant to the antibiotics that are commonly used to treat bacterial infections. It can
transmit from person to person through contact or contaminated objects. In practice two types of
MRSA infections have been recognized, Hospital-associated MRSA (HA-MRSA) and Community-
associated MRSA (CA-MRSA)1
(Zeller, Burke, & Glass, 2007). MRSA has become a huge public
health concern because of its increasing prevalence and eventually increasing morbidity & mortality
and economic burden2
(Lodise & McKinnon, 2007). In 2003, total expenditure of $14.5 billion and
$12.3 billion was attributed to inpatient and surgical patient stay respectively due to infection caused
by Staphylococcus aureus3
(Noskin, et al., 2007). Figures show that a single MRSA case costs $2277
to $3200 to third party payers and $7070 to more than $20,000 to society. Furthermore, figures
indicate that annual burden of MRSA ranges from $478 million to 2.2 billion. This has created a need
to develop public health policies to prevent and treat MRSA. Various studies have been performed to
understand the trend of MRSA. The purpose of this paper is to discuss four major study designs,
namely cross-sectional study, case-control study, retrospective cohort study and randomized control
trial, to study MRSA and hospital readmissions.
Cross-sectional study Design4
(Warshawsky,et al., 2000)
It has been found that hospital patients and visitors experiencing methicillin-resistant
Staphylococcus aureus or MRSA and its related symptoms has increased dramatically in the last
three decades. In this particular cross- sectional design the overall objective was to determine the
prevalence of certain risk factors associated with the occurrence of MRSA in the known hospital
settings and into the community. The incidence of people who had been infected with MRSA,

3. specifically those who had been hospitalized before, were evaluated to determine what risk
factors were increasing the spread of the infection.
The study’s objectives were clear, and they chose to obtain them by testing people in an
area experiencing an epidemic of a new strain of MRSA. The design allowed for a testable
outcome and served to help explain the problem. The purpose of this study was concisely stated
and agreed with the title. It was limited to the researchers’ capabilities and resources in collecting
the necessary data, however, the study was well maintained and researched.
To assess what potential risk factors were associated with this possibly fatal ailment three
acute-care teaching hospitals, two chronic care hospitals, 20 long term care facilities, one public
health laboratory, and three private laboratories participated in the study to screen and evaluate
the patients within London, Ontario. There was no alteration in the screening processes
performed by the facilities and patients were screened for MRSA colonization at admission into
specific wards in the hospitals which led to the screening of those in contact with the patients
found to have the infection upon re-admission arrival. Two surveys were created for the acute-
care hospitals and for those “community- diagnosed” MRSA patients, those that were not
inpatients or outpatients of the hospitals when the MRSA infection was identified. Rarely
patients were interviewed after practitioners extracted their necessary data from their medical
charts. Little information was collected for those patients who were earlier noted in being MRSA
positive. Newly acknowledged participant’s demographic information such as age, gender,
ethnicity, occupation, hospitalization, past antibiotic use and underlying medical conditions, also
considered risk factors, were used to collect and analyze data to identify a specific source.
The methods used to gather the data for this article were clearly explained. The
instruments and development were explained, and the reliability coefficients of all possible tests

4. were given. The population used was adequate in estimating the level at which the infection
reaches particular patients in a given environment. There was not any extensive discussion of the
statistical techniques given in this particular section. By using a cross- sectional design to
research and measure this subset of the population, the study helped to create a more
standardized approach in evaluating MRSA.
Over the course of the study 337 people were newly diagnosed as infected or colonized
with MRSA. An overall annual incidence of 100/100,000 at a 95% confidence interval was
established in the residents. 211 people were patients in acute- care hospitals, 120 community-
diagnosed, 59 from long term care facilities, 34 MRSA positive people were identified in
physician’s private practices, and 27 in chronic care hospitals. Most of the MRSA diagnosis
occurred in people 70 years old and over, with men having a slightly higher prevalence than
women.
These results confirmed the increased necessity of knowledge into what MRSA is and
does within hospitals and now communities.
The study concluded that the rate of MRSA expansion from hospitals, long-term care
facilities, and community physician’s offices into communities was remarkably higher than what
was previously reported. It was also found that those individuals who had experienced a short to
increased duration in a medical facility had more contact with the infection which caused this
risk factor to be the single most important risk associated with contraction of certain MRSA
strains. The study determined that screening for MRSA in patients who have previously been
hospitalized before re-admittance was necessary to combat and indirectly lessen the frequency of
the infection in most cases.

5. There are also a few limitations to this particular cross sectional design. The screening of
patients was done upon admission and did not account for those individuals who were already
admitted and experiencing the MRSA bacteria. 37% of isolated patients who were found to have
MRSA were tested as a secondary notion behind their other diagnostic tests i.e. not all patients
were swabbed to find if they had contracted the infection, leaving many without any tests
positively or negatively indicating the presence of MRSA.
This was a very in-depth research project, particularly because of its thoughtfulness. For
the most part, it was well written and well organized. There was a definite need for a short
review of literature to develop the situation. The article accurately evaluated this particular strain
of the MRSA infection and how it is typically found in older adult males who have spent some
time in a hospital environment. Overall, it was a very interesting, significant contribution to the
field of research.
Case-control study design5
(Fukuta,Cunningham, Harris, Wagener,& Muder, 2012)
Investigators carried out this study to identify risk factors for developing methicillin resistant
Staphylococcus aureus (MRSA) infection among patients already colonized with MRSA on hospital
admission. The authors provided ample background information on the need to carry out this study
and why it was important to identify risk factors for developing MRSA infection in patients already
colonized with MRSA during hospitalization as no studies have been done in this regard to identify
high risk MRSA colonized patients who may benefit from decolonization.
The type of design used to carry out this study was case-control. A case control study is an
effective study design used to assess risk factors associated with a disease. This was an appropriate

6. design since the research was aimed at studying the risk factors and exposures that would increase
the likelihood of patients already colonized with MRSA who were later infected with the bacteria.
Unfortunately, the researchers in this study failed to acknowledge the shortcomings in using
a case control study when performing this research. They failed to say that the results achieved at the
end of the study should have been taken as a foundation for a more detailed cohort study which
entails the study of a specific exposure. Cohort study would provide a stronger test of association
between the exposure and the relative risk of developing MRSA infections in MRSA colonized
patients on hospital admission.
Also, the case control study design was flawed because of its long duration. How possible is
it to store samples from 2003 to 2011 before they were analyzed? This raises questions about the
study design and methods used to conduct the study. The Investigators seem to occasionally abandon
their study design which is a case control study and drifting more to a cohort study. There was also
inconsistency with the authors’ aims and objectives which were: to determine the incidence and risk
factors of MRSA infection- which is not in accordance with a case control study.
The investigators were also inconsistent with the inclusion criteria used in selection of cases.
Cases for this study were picked from patients admitted initially to the surgical floor on which
MRSA surveillance was first initiated. This was later expanded to include patient admitted into the
surgical ICU. The inclusion criteria for cases was again expanded to include all patient admitted to
the entire acute care division.
Controls were randomly picked from Veterans Affairs Pittsburgh System (VAPHS) hospital
database who had MRSA colonization. Pairing of cases to controls was adequate (each case patient
was matched with two non-infected control subjects randomly selected from the same database).
However, criteria for matching the cases and controls was not adequate as they were matched by
calendar year of admission only.

7. The authors did not mention the total number of participants in the study. The materials and
methods were inconclusive about the number of cases and controls recruited to participate in the
study. This was only mentioned in the result of the study.
The risk factors of interest were measured with the odds ratio in keeping with standard practice
for the determination of risk in a case control study. The risk factors the research tried studying were:
 ICU admission
 Prior History of MRSA infections and colonization
 Presence of an open wound and
 Presence of a central venous catheter and the frequency of undergoing invasive procedures
 Transfer from a nursing homes
The study revealed that admission into the ICU was a significant risk factor for developing
MRSA infection. Patients who had difficulty swallowing, an open wound, and a central venous
catheter were also at high risk of developing MRSA. This was also true for patient with prior history
of MRSA infection or colonization. There was also a positive association and increased risk of
developing MRSA infection in patients coming from long-term care facilities. The results also
suggested that patients undergoing invasive procedures may benefit from decolonization.
As pointed out in the earlier aspect of the critique, the study had shortcomings, these
shortcomings were a source of error in the results and reduces the potential for its application in real
life situations and to a more diverse population.
The author recognized that there were some limitations in the study. Firstly, the author
acknowledges that despite the high sensitivity associated with using nasal swab sampling as a
screening tool (as suggested in a previous study), they may have failed to identify some MRSA-
colonized patients. Secondly, the patient population that was studied changed over time and MRSA

8. surveillance was initiated on a single unit and was later introduced to other units. Finally, the authors
recognized that this study was performed in a single VA hospital and as such, the result may not have
been applicable to populations that were more diverse.
One of the major limitations to this study that was evident, was a lack of uniformity with the
cases due to changes in criteria used in their selection for the study over time. This problem would
probably have led to results that have little application in real life setting.
The study was worth the effort because MRSA is a disease of public health importance due to
its high morbidity, and the high cost of healthcare associated with MRSA infections. Also, knowing
the factors that increase the risk for the MRSA infection can help reduce the high morbidity of this
disease and ease the cost of treating it.
Retrospective cohort study design6
(Emerson,et al., 2012)
The third study design is a retrospective cohort study. Objective of the study is to investigate
the time period between acquisition of hospital-associated infection and hospital readmission.
Investigators used a retrospective cohort of adult patients based on their exposure status and studied
the incidence/event, which is hospital readmission in this case. Retrospective cohort study is an
appropriate design for this study because authors aim to study the outcome based on the exposure.
Data collected includes patients’ administrative, laboratory and pharmacy records collected and
maintained by UNMC over a period of 8 years. Primary exposure of interest is a positive clinical
culture for one of the three hospital associated pathogenic organisms obtained more than 48 hours
after hospital admission. Primary outcome of interest is the time to the hospital readmission.
Appropriate measures have been implemented to avoid any duplication of data and adjustment for
lost to follow-up cases.

9. Over an 8 year time period, ranging from January 1, 2001 to December 31, 2008, 136,513
index hospital admissions out of 244,852 total admissions in UNMC were considered for the study.
108,339 patients were excluded from the study because they did not meet the inclusion criterion. This
is an adequate sample size to conduct a retrospective cohort study.
Appropriate single variable, bi-variable and multivariable statistical methods have been
employed to analyze the data and assess the outcomes. The purpose was to test the hypothesis that a
positive clinical culture for one of the three HAI pathogens (MRSA, Vancomycin-resistant
enterococci, Clostridium difficile) was associated with shorter time period to hospital readmission.
Various parametric procedures, such as Student t test and nonparametric procedures, such as
Wilcoxon rank sum test were conducted to examine normally distributed and non-normally
distributed continuous variables respectively. Chi-square analysis was performed to examine discrete
covariates for association with both outcome and exposure. Age was found to be significant, both as
a continuous as well as categorical variable. Therefore, age has been recoded as a dichotomous
variable at 65 years of age to make the interpretation simple. Another important predictor, length of
hospital stay has been dichotomized about the median due to its highly skewed distribution. Survival
analysis for patients with hospital readmission was conducted using Kaplan-Meier method, Cox
proportional hazard model and log rank test statistic. Standard 0.05 has been taken as the level of
significance (alpha) to test the two sided hypothesis.
Authors concluded that the patients with positive hospital acquired infection cultures tend to
have shorter time to hospital readmission. This adds to increased healthcare costs and eventually
increased economic burden. Furthermore, authors suggest that policies should be designed and
implemented to provide additional discharge planning resources to those patients who have a positive
HAI culture 48 hours after hospital admission. The conclusion is in compliance with the statistical
analyses’ results and is therefore accurate.

10. Investigators did mention some limitations of the study. According to the article, a large
number of hospital admitted patients with positive clinical culture for HAI were excluded from the
study either due to death or their failure to meet 48 hours after hospital admission cut off point
criterion. Moreover, the data used was administrative data and lacked the information on origin of
infection. Also, there was no information on the patients who got readmitted to other health care
facilities.
However, there are a few limitations of the study that are not mentioned in the article. The
study has been conducted using data from only one medical center. Therefore, it is not appropriate to
generalize the results of the study to entire population. This might lead to ecological fallacy. Another
limitation is that the outcome of interest is time to hospital readmission. Data has been adjusted for
age, sex, length of index hospital stay, ICU stay, year of hospital admission and Charlson
comorbidity index. There is no information about patients’ life style habits, hygiene, diet, occupation,
and other environmental factors that can act as confounders. Furthermore, the article uses some
unconventional sentences/phrases in discussion section that fail to convince the readers, such as “to
our knowledge, only one earlier study has examined the association between positive clinical culture
and hospital readmission”, “authors believe that”.
Although the study has a few limitations, it can still be considered as a good study because of
its large sample size. In addition to that, data collected over a long time period controls for the
fluctuations of prevalence of HAI and health care policy issues.
Randomized control trial7
(Huang SS, 2013)
The final study design is a randomized control trial. Objective of the study is to the best
method to prevent ICU infection, particularly that from MRSA. A cluster randomized practical

11. trial has been used for this study. They allotted different hospitals, and all the ICU patients in it,
to one of three strategies: “Group 1 implemented MRSA screening and isolation; group 2,
targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and
group 3, universal decolonization (i.e., no screening, and decolonization of all patients).”
As mentioned in the textbook, RCTs are considered gold standard of study designs. To
support or assess clinical evidence and public policy, they are at the top of the list when
considering quality. Randomized control trial is an effective study design to understand these
interventions, as the authors aim to find the most practical and effective way of preventing
MRSA infections. Information for each hospitalization day was collected, including pharmacy
records and blood cultures. Primary outcome of interest was ICU-attributable, MRSA positive
clinical cultures.
The baseline period was 12-months, followed by a phase-in period and finally an 18-
month intervention period. 43 hospitals having 74 ICUs and 74,256 patients participated in the
intervention and underwent randomization. This number seems adequate for a randomized
control trial. “Reasons for noncompliance included discharge before scheduled bathing or
Mupirocin administration, discharge before MRSA-positive results were obtained, length of ICU
stay of less than 1 day, and patient’s decision to decline the intervention.” There were three
hospitals (out of a total of four) which performed marrow and organ transplantation, in group 3.
It was a fortunate chance, as they accounted for increased risk.
Appropriate multivariable covariate-adjusted statistical methods were used to analyze the
data and assess the outcomes. The trial was based on the rarest of outcome, MRSA bloodstream
infections, which showed a greater difference amongst the three strategies. The study was
adjusted for hospitals in states mandating MRSA screening in the ICU, models that excluded the

12. small numbers of medical-only and surgical-only ICUs, age, sex, race, insurance type, and co-
existing conditions.
As the case-control study revealed, admission into the ICU, and undergoing invasive
procedures were significant risk factors for developing MRSA infection, and may benefit from
decolonization. Authors concluded that universal decolonization resulted in a significantly
greater reduction in the hazard of MRSA positive clinical cultures than did screening and
isolation or targeted decolonization. Additionally, universal decolonization eliminated the need
of MRSA surveillance tests and associated reduction in contact precautions. However, the
authors have mentioned that these findings have impact on legislative mandates that require
MRSA screening.
There were a few drawbacks of this study that the authors have claimed. They have not
provided any information about using Mupirocin or Chlorhexidine alone, compared to using
them in combination. The bigger problem with this strategy is the universal decolonization
resulting in widespread use of Chlorhexidine and Mupirocin, which could in turn cause increased
resistance.
The research was undertaken to generalize the results to a broad set of hospitals, mainly
community hospitals. Due to the large sample size and multiple centers involved, I think, the
study was successful in achieving that aim. “The authors found that universal decolonization
prevented infection, obviated the need for surveillance testing, and reduced contact isolation.
However, if this practice is widely implemented, vigilance for emerging resistance will be
required.”
Conclusion

13. Cross-sectional studies clearly explain that those individuals who had experienced a short to
increased MRSA rate duration in a medical facility were more prone to the infection which caused this
risk factor to be the single most important risk associated with contraction of certain MRSA strains.
Therefore, indicating the strengths of answerable objectives in this particular study design. On the other
hand, case control study is also an effective solution in assessing risk factors related to a disease. Case-
control studies do, however, require long durations which is their major weakness due to the
inconsistency of the associated outcome. As noted earlier, we can conclude that the randomized control
trial studies are the gold standard of study designs which have effectively decreased the rate of ICU
MRSA infections among individuals. In addition, randomized control trials are also supportive in
assessing clinical evidence and public policy; they are at the top of the list when considering quality.
Moreover, randomized control trials are effective study designs leading to greater understanding and
effectiveness of interventions preventing the spread of MRSA infections. With that said, randomized
control trials have also contributed to the universal decolonization of MRSA with the widespread use of
Chlorhexidine and Mupirocin, which could contribute to the increased resistance by the bacteria.
Ideal Study Design
Both Cohort and Case-Control Study designs are appropriate to analyze the association between
Hospital Associated Infection (HAI), specifically MRSA, and hospital readmission. However, we prefer
Cohort instead of Case-Control design in this case because Cohort study provides a stronger measure of
association between exposure, which in this case is MRSA and hospital readmission, which is outcome in
this case. Also, retrospective cohort study gives an added incentive of being less time-consuming and
inexpensive study design. With Cohort Study design we can study a single exposure in relation to a
particular or multiple outcome/disease/event (hospital readmission in this case) while Case-control
studies we can study a particular outcome in relation to single/multiple exposures.

14. Future Research Possibilities
The control of community MRSA infections is an extraordinary challenge, requiring improved
surveillance, contact tracing, education, and treatment of both infected cases and colonized contacts.
There are severalways that remain under exploration. The actual burden of disease caused by MRSA
remains massively unknown. Moreover, there is still irreconcilable evidence with respect to key questions
concerning the most cost-effective methods for control of the endemic of MRSA. Since MRSA is a
concern for everyone around the world, interventions that may decrease the likelihood of recurrent MRSA
infections are spread onto an individual: decolonization protocols, cleaning of fomites, antibiotic
therapies, and vaccines are all potentially relevant avenues for the future control of MRSA in the
community. Each of these modalities will require more studies to evaluate its efficacy and safety. The
future of MRSA Research will determine how frequently these patients have recurrent MRSA infections,
how commonly they seek medical attention for the infections, the presence of the risk factors for
reinfection listed above, and the genotypes of MRSA strains associated with infections and any identified
asymptomatic colonization to assess the role of chronic colonization in the recurrence of MRSA
infections.

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