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Clinical outcomes involving patients that develop septic arthritis with methicillin sensitive staphylococcus aureus versus methicillin resistant staphylococcus aureus
⁎Corresponding author: Kyle Cox. kyle.cox7@knights.ucf.edu
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Septic Arthritis is an orthopedic emergency that requires prompt diagnosis and treatment. Staphylococcus aureus is the most common pathogen causing septic arthritis. This review seeks to describe clinical characteristics and outcomes associated with patients with methicillin-resistant (MRSA) vs. methicillin-sensitive staphylococcus aureus (MSSA) septic arthritis. The review showed that those infected with MRSA were older, had more chronic medical conditions, and higher values of inflammatory markers. MRSA septic arthritis was also associated with more complications, longer duration of antibiotics, and increased mortality. Thus, health care providers should maintain a high index of suspicion, diagnose, and treat aggressively to prevent adverse outcomes.
Keywords
Septic arthritis
MRSA
MSSA
Outcomes
1 Introduction and background
Septic arthritis is an infection of a joint cavity, and is an orthopedic emergency that requires prompt diagnosis and treatment. The infection can lead to rapid joint destruction and associated morbidity and mortality. Septic arthritis encompasses infection of the joint caused by bacteria, fungi, mycobacteria, or viruses. Bacterial joint infections are the most common.1 Septic arthritis usually presents as a mono-microbial infection, but can also present as a poly-microbial infection. Bacterial septic arthritis is estimated to account for 8–27 percent of acutely painful joints in adults.2 Risk factors for development of septic arthritis include: age greater than 80, diabetes mellitus, rheumatoid arthritis, presence of a prosthetic joint, recent joint surgery, concurrent skin infection, intravenous drug use, and recent intraarticular corticosteroid injection.3
Overall, Staphylococcus Aureus is the most common pathogen that causes septic arthritis.4 Septic arthritis can be caused by both Methicillin Sensitive Staphylococcus Aureus (MSSA) and Methicillin Resistant Staphylococcus Aureus (MRSA). MRSA infection prevalence has increased with the continuously increasing amount of antibiotic resistance.5 MRSA infections can present as both hospital acquired and community acquired infections.
Despite the known fact that septic arthritis can be caused by both MSSA and MRSA, there have been a limited number of studies that examine the difference in clinical characgeristics and clinical outcomes of patients that develop septic arthritis caused by these two causative agents. This review aims to stratify the risk of cases of septic arthritis caused by MSSA versus MRSA in order to guide clinicians on management and expected clinical outcomes associated with these microorganisms.
The available literature was searched using the PubMed database with keywords: “septic,” “arthritis,” “MSSA,” “versus,” “and,” “MRSA,” “outcomes.” Articles that compared cases of septic arthritis in individuals of any age caused by MSSA and MRSA were included. Endpoints for this review included clinical outcomes including but not limited to: length of hospital stay; length of antibiotic treatment required; number of operations required; disease recurrence; and sepsis related mortality. 8 papers were identified that fit the aforementioned criteria. A critical appraisal was performed for each article and the methodology and results of the papers are reported in the subsequent review section. Differences in rates of the aforementioned outcomes; relative risk values; odds ratios; confidence intervals; and the corresponding p-values for each article were included in the review of each article.
2 Review
2.1 Article 1: methicillin resistant staphylococcus aureus versus methicillin sensitive staphylococcus aureus adult haematogenous septic arthritis6
A retrospective analysis was performed on all patients presenting to Leeds Teaching Hospital over a five year period with adult hematogenous septic arthritis. The patients included were from primary and tertiary referrals. There was no uniform early time that all patients were enrolled due to the retrospective nature of this prognostic study. All patients that met the inclusion criteria were assessed for clinical outcomes of their septic arthritis for 1year of follow-up. There is clear definition of the outcomes assessed between MSSA and MRSA groups, but there is no mention of blinding the researchers that evaluated the data and determined the clinical outcomes between the two groups. There were no sub-groups with different prognoses identified therefore there was no adjustment for different prognoses between subgroups.
The results were reported as percentages of the two sub-groups that developed a specific clinical outcome (eg. operative outcome, antimicrobial duration, recurrence, sepsis related mortality). These outcomes were assessed in the one year follow-up for all eligible patients. Continuous variables were analyzed using Student’s t-test and dichotomous variables were analyzed using Fisher’s exact test. There were no reported 95% confidence intervals in this study, but significant results correspond to a p-value <0.05. MRSA patients were significantly older, more likely to have a nosocomial infection, have more chronic medical conditions, and had a stronger association with end-stage renal failure. MSSA patients were significantly more likely to be intravenous drug users. MRSA patients were significantly more likely to be treated with inappropriate empirical antibiotics. MRSA patients did have a strong trend towards a higher all cause 6 month mortality rate than MSSA patients.
2.2 Article 2: changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant staphylococcus aureus7
This retrospective chart review conducted at Le Bonheur Children’s Medical Center at the University of Tennessee Health Science Center in Memphis, Tennessee between 2000 and 2004 included children diagnosed with acute hematogenous osteoarticular infections. All patients enrolled in the study must have had no more than 14days of symptoms prior to presentation at the hospital. Patient records were obtained throughout the duration of their hospitalization until discharge. The goal of this study was to determine total and pathogen-specific incidence rates of acute hematogenous osteoarticular infections and to compare clinical and demographic features of children with MRSA infections with those with MSSA infections. Outcomes were clearly defined as duration of symptoms before clinical presentation, laboratory parameters upon admission and follow-up, number of calendar days in the hospital, number of calendar days with fever and positive blood cultures, culture results, radiographic assessments, surgical and non-surgical procedures, antimicrobial therapy, complications, duration of therapy and short-term outcomes. There were no prognostic factors that were adjusted for in this study.
Data was analyzed using Kruskal-Wallis tests, χ2 analysis, or Fisher exact test where appropriate. Results showed increasing incidence of total infections but the rate of MSSA infections remained constant throughout the course of the study while the rate of MRSA infections increased from 4%-40%. There were no differences in the duration of fever or pain before the diagnosis. There was significantly increased risk for subperiosteal abscess formation, requirement of surgical procedures, and mean length of hospital stay in patients with MRSA infections as compared to those with MSSA infections. However, there was no increase in the rate of developing chronic osteomyelitis despite the increase in the severity of community acquired MRSA infections. This study reported that 46 of 47 MRSA infections in the community of focus were susceptible to clindamycin. Ultimately, this study recommended that careful evaluation for subperiosteal and muscle or soft-tissue abscess as well as other complications must be conducted to ensure prompt resolution of MRSA infections, which are potentially life-threatening. This study recommends antibiotic coverage of MRSA in empiric management of osteoarticular infections, though antibiotic susceptibility in your respective communities should drive the choice in antibiotic.
2.3 Article 3: community-acquired methicillin-resistant staphylococcus aureus musculoskeletal infections: emerging trends over the past decade8
This is a retrospective chart review conducted at Children’s Hospital of Philadelphia, a tertiary-care children’s hospital, between 2001 and 2010 that included previously healthy children and adolescents below the age of 19 years of age with acute musculoskeletal S. aureus infections. The goal of the study was to identify epidemiological trends of MRSA and MSSA infections in the Philadelphia community over a decade by comparing patient age, gender, infection type, dates of admission and discharge, MRI studies, CRP levels at presentation, number of surgical procedures performed, antibiotic treatment regimens, length of inpatient treatment, and complications during hospitalization between the two groups. There is no uniform early time that all patients were enrolled in this study due to the retrospective nature of the study. Patient records were obtained and the follow-up period was the length of the patient’s hospital stay. The outcomes in this study were clearly defined, however there was no mention of blinding the researchers to the clinical outcomes described in this study. There was no adjustment for different prognostic factors between the two groups.
Patients were divided into two cohorts for data analysis: culture positive MRSA and culture positive MSSA. The data were analyzed by using a 2-sample Student’s t-test and Mann-Whitney U test for continuous variables and Pearson χ2 test was used to compare categorical data. A p-value <0.05 was considered statistically significant. The prevalence of patients with culture positive MRSA infections in the community of focus increased threefold over the studied 10year period. MRSA infections were also associated with a significant increase in CRP levels at admission, length of hospital stay, and number of surgical interventions. These results increase awareness of these rising trends and provide a scaffold to counsel patients and family members on the increased risk for complications and other sequelae posed by MRSA infections.
2.4 Article 4: adult native septic arthritis in an inner city hospital: effects on length of stay9
A retrospective analysis of all patients presenting with native joint infections between 1999 and 2008 were identified. It is unclear whether the patients included were from a primary or tertiary center. There is no uniform early time that all patients were enrolled due to the retrospective nature of this prognostic study. There is no mention of the length of follow-up. The study primarily examined the length of hospital stay between the different infectious organisms and did not examine any other clinical outcomes, so it seems as though length of follow-up is not applicable in this study. There is clear definition of the outcome assessed (length of stay) between MSSA and MRSA groups, but there is no mention of blinding the researchers. The study did adjust for prognostic factors including past medical comorbidities.
The results were reported as length of stay between the different groups of patients including those with MSSA and MRSA infections. Spearman’s correlation and Mann Whitney U-Tests were performed to assess for statistically significant difference between the two groups in regards to length of stay after developing the infection. Confidence intervals for the length of stay between groups with MSSA and MRSA were not reported. There was no statistically significant difference in the length of stay between patients with MRSA and MSSA septic arthritis. Sub-groups were analyzed based on medical comorbidities, age, sex, and ethnicity. After sub-groups were analyzed there was no statistically significant difference between lengths of stay between the sub-groups.
2.5 Article 5: High prevalence of methicillin-resistant staphylococcus aureus among patients with septic arthritis caused by staphylococcus aureus10
This is a retrospective chart review from two branches of Chi Mei Medical Center in Tainan, Taiwan included 93 culture-confirmed cases of S. aureus septic arthritis between 2008 and 2011. This review does not specify the duration of time these patients were studied during their clinical course, although follow-up was not necessary due to the retrospective nature of this study. Patients with culture confirmed MRSA infections were compared against patients with culture-confirmed MSSA infections with regards to patient age, gender, underlying conditions, laboratory data, microbiological findings, antimicrobial susceptibility test results, and patient outcome (although there is no specification regarding what these outcomes are). There were no adjustments made for differences in prognostic factors between the two groups studied.
Continuous variables were compared using the Wilcoxon rank sum test or Student’s independent t-test. Categorical variables were compared using χ2 test or Fisher’s exact test. P value <0.05 and was considered to represent statistical significance. Results of this study showed that MRSA infections were more likely to occur in patients greater than 65 years of age and were more likely to occur in healthcare-associated infections. The majority of infections in both groups were community acquired. No significant differences in gender, type of infection, underlying conditions, cause of arthritis, treatment, or outcomes were identified between the two groups. This study found no significant difference in mortality. The overall incidence of MRSA infections has increased in this community of patients and is considered an emerging pathogen that is contributing to antibiotic resistance. Thus, this study emphasized the importance of infection control measures, including hand hygiene, contact isolation, and use of antibiotics in patients with confirmed MRSA infections, especially in elderly patients greater than 65 years of age.
2.6 Article 6: septic arthritis due to methicillin-resistant staphylococcus aureus in adults11
This is a retrospective analysis performed on patients developing septic arthritis in peripheral joints from 1984 to 2011 from the tertiary level hospital Universitaria Germans Trias I Pujol in Barcelona, Spain. The patients included were older than 18 years of age and had a synovial fluid culture positive for MRSA or MSSA during this time period. All patients that met the inclusion criteria were assessed for clinical outcomes, but the follow-up time was not specified. There is clear definition of the outcomes assessed between MSSA and MRSA groups, but there is no mention of blinding the researchers. There was no adjustment for different prognoses between subgroups.
The statistical analysis was performed using nonparametric tests, Fisher’s test, and χ.2 Statistical significance was set at p<0.05. The results were reported as percentages of the two groups that had a specific characteristic or developed a specific clinical outcome. MRSA patients presented at an older age, were more likely to have an underlying neoplasm, and had more positive blood cultures. MSSA patients were more likely to be treated with appropriate empirical antibiotic therapy. There were no reported 95% confidence intervals in this study.
2.7 Article 7: community-associated MSSA and MRSA bone and joint infections in children: experience from India12
This was a retrospective study of 74 patients under the age of 18 who presented to a single tertiary hospital in India between 2004 and 2008 with invasive, community-acquired S. aureus bone or joint infections. Patients who met the inclusion criteria were analyzed to identify demographic trends within their community, clinical presentation, hospital course, and antibiotic susceptibilities between patients with MSSA and MRSA infections. Patients were not included if they met any one of the exclusion criteria. Follow-up in this study lasted from the time of admission until hospital discharge. Outcomes were clearly defined between MSSA and MRSA groups, however there is no mention of blinding the investigators to clinical outcomes of the two groups. The researchers did not adjust for prognostic differences between the two groups.
Statistical analysis was carried out using χ2-tests for proportions and t-tests for continuous variables. P-value <0.05 was considered statistically significant. The investigators also used the data to predict a clinical algorithm that will help to identify MRSA infections from MSSA infections. Patients with MRSA infections had a higher prevalence in the studied population and was associated with higher erythrocyte sedimentation rate (ESR), c-reactive peptide (CRP), and absolute neutrophil count (ANC). Patients with MRSA infections experienced longer hospital stay, longer duration of febrile days, and longer antibiotic course resulting in increased risk for disability and death. Predictive criteria for MRSA infection was determined as hemoglobin concentration <9.5g%, hematocrit <34%, ESR >35mm/h, CRP >32mg/dl, white blood cells >14,000 cells/109l, and ANC >65% with 92% probability of MRSA infection when all 7 criteria are met. Patients infected with MRSA are at a significantly increased risk for morbidity and mortality, therefore early diagnosis when there is a high degree of suspicion and more aggressive antibiotic and potential surgical debridement is necessary to prevent the associated morbidity and mortality.
2.8 Article 8: a large multicenter study of methicillin–Susceptible and methicillin–Resistant Staphylococcus aureus prosthetic joint infections managed with implant retention13
A retrospective observational analysis performed in 17 hospitals in Spain between 2003 and 2010 with prosthetic joint infection caused by S. aureus. All patients that met the inclusion criteria were assessed for clinical outcomes, and the follow-up time was not specified. However, patients were not included if the patient met one of the failure criteria. There is clear definition of the outcomes assessed between MSSA and MRSA groups, but there is no mention of blinding the researchers.
There was no adjustment for different prognoses between subgroups. Comparative analyses were performed with X2 or Fisher's test for categorical variables, and the Mann-Whitney U-test for continuous variables. All analyses were two-tailed with 95% confidence intervals, and a p-value <0.05 was considered statistically significant. MRSA infections were more common in older patients, more frequently had chronic renal impairment, and were more likely to fail antibiotic therapy. This study demonstrated significant clinical outcomes differences between patients developing MSSA vs. MRSA septic arthritis after prosthetic joint infection and can be used for risk-stratification and guide management and follow-up for patients developing septic arthritis infections with these specific micro-organisms.
3 Conclusions
Septic arthritis is an orthopedic emergency and the treatment is dependent on the specific causative organism. Septic arthritis is commonly caused by MSSA or MRSA. This review highlights the differences in clinical characteristics and outcomes associated with the different infectious etiologies so that healthcare providers can manage treatment appropriately and allow for risk stratification for future treatment.
Review of the 8 presented articles comparing MRSA and MSSA septic arthritis found that these groups differ in the following clinical characteristics. MRSA patients were significantly older, more likely to have a nosocomial infection, have more chronic medical conditions, had a stronger association with end-stage renal failure, had a significant increase in erythrocyte sedimentation rate (ESR), c-reactive peptide (CRP), and absolute neutrophil count (ANC) levels at admission, more likely to have an underlying neoplasm, and had more positive blood cultures. MSSA patients were significantly more likely to be intravenous drug users. Finally, there were no differences in the duration of fever or pain before the diagnosis of either MRSA or MSSA.
Review of the 8 presented articles comparing MRSA and MSSA septic arthritis found that MRSA and MSSA differs in the following clinical outcomes. MRSA septic arthritis was associated with an increased number of surgical interventions, longer duration of febrile days, and longer courses of antibiotics. In fact, MRSA infections were found to be more likely to be inadequately treated and/or fail antibiotic therapy when compared to MSSA infections. As a result of this, Al-Nammari et al. found that patients with MRSA infections were more often treated with inappropriate empiric therapy. There were some contradictions in the data, however. The majority of studies showed that MRSA infections were associated with longer hospital stays when compared to MSSA infections, but Daynes et al. showed that there was no statistically significant difference in the length of stay between these groups. More importantly, while most of the studies showed that MRSA infections were associated with an increased risk of all-cause mortality, Lin et al. found no significant difference in mortality between the groups. Overall, the studies agreed that MRSA infections predisposed patients to increased mortality, whether iatrogenically or pathologically, which increased the risk of disability in these patients.
One limitation is that some of the articles reviewed combined results regarding septic arthritis with other types of musculoskeletal infections such as osteomyelitis. Another limitation is the included studies pertained to both adult and pediatric populations. Finally, microorganisms had different antibiotic susceptibilities depending on the specific community being studied. Across all studies, the prevalence of MRSA septic arthritis increased significantly throughout the studied time periods, thus illustrating the importance of identifying these patients and treating them accordingly. Healthcare providers should have a high index of suspicion for MRSA septic arthritis with the hopes of obtaining more aggressive diagnosis and therapy in order to prevent adverse clinical outcomes.
Conflicts of interest and source of funding
None were declared by the authors.
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