Methicillin-Resistant Staphylococcus aureus Colonization and Empyema: Does it Matter?

Abstract

Background:

The relation between MRSA colonization and empyema culture results is unknown. We hypothesized that MRSA-colonized patients would be more likely to develop MRSA empyema, and sought to determine if MRSA culture positive empyema had an effect on clinical management or patient outcomes.

Methods:

The medical records of patients with a diagnosis of empyema from 2007–2010 were retrospectively reviewed for demographics, MRSA colonization status, comorbidities, culture results, clinical management, and discharge disposition. The relationship between MRSA colonization status and culture results was analyzed by bivariate testing. Logistic regression was utilized to determine relations between empyema culture results, comorbidities, and clinical course.

Results:

Of 147 patients identified with empyema, 16 (10.8%) were MRSA colonized. Colonized patients had substantially higher rates of MRSA-positive empyema cultures (75% vs. 4.6%; p<0.001). A greater percentage of the MRSA-positive empyema patients 66.7% were managed with tube thoracostomy alone, compared with culture positive patients with an organism other than MRSA and those with negative cultures (39% and 34% respectively; p=0.043). Neither empyema culture results nor colonization status were substantial risk factors for poor discharge (skilled nursing facility, long-term care hospital, or death).

Conclusions:

MRSA-colonized patients hospitalized with empyema are highly likely to have cultures positive for MRSA.

Staphylococcus aureus commonly colonizes the nares and can alter the rates of infection of the aerodisgestive tract leading to pneumonia and parapneumonic empyema. With the emergence of methicillin-resistant S. aureus (MRSA), there is concern for severe pulmonary infections with this antibiotic-resistant organism. MRSA is an increasingly important pathogen in both community and hospital acquired infections with overlap of the strains [1]. MRSA colonization rates have been increasing and current rates are estimated at 0.2–4.1% for the general population, and 6–13% for patients admitted to the intensive care unit [2 –5]. Antibiotic-resistant bacteria including MRSA are responsible for up to 60% of hospital-acquired empyemas [6,7]. Colonization is the strongest risk factor for development of Staphylcoccus aureus infection for nosocomial infections such as central line associated blood stream infections and surgical site infections [1,5,8–9]. MRSA in the surgical incisions of patients with post-operative infections is more frequently isolated in MRSA carriers, and decolonization protocols can reduce surgical site infections in this population [10 –12]. Nasal-swab testing effectively identifies MRSA-colonized patients.

Empyema is a common reason for surgical consultation in patients with complications of pneumonia and carries a mortality rate near 20% [6]. Management strategies include tube thoracostomy combined with antibiotics followed by surgical decortication if residual loculated fluid collections, thickened pleura, or trapped lung persist. Instillation of tissue plasminogen activator (tPA) or other fibrinolytic enzymes has been shown to decrease the need for surgical intervention when performed in early stage empyema [13–14].

Pleural infections because of S. aureus, gram-negative or mixed aerobic organisms have a higher mortality rate than streptococcal bacterial growth [6]. Antibiotic management is tailored to cover bacteria based on pleural culture results. However, only 60% of pleural fluid cultures identify a specific organism and therefore antibiotics often must be chosen empirically [7]. Inability to tailor antibiotic regimens may potentiate further drug resistance in bacterial species.

The relation between MRSA nasal colonization and empyema is unknown. We hypothesized that MRSA colonized patients would be more likely to have MRSA positive cultures. As secondary endpoints, clinical management and discharge disposition of colonized and non-colonized patients were evaluated.

Patients and Methods

From 2007 to 2010 all patients with the diagnosis of empyema (ICD-9 codes 510.0 or 510.9) or patients that underwent surgical empyema management (procedure code 34.04, 34.06, 34.51, or 34.52) were abstracted from hospital records. All hospitalized patients during this period were screened for MRSA colonization by nasal swab within 48 h of admission according to institutional policy. Nasal swabs were performed based on a previously described protocol [15]. Patients who were positive for MRSA colonization were placed on contact isolation precautions for the duration of their hospital stay in order to prevent nosocomial spread of infection. After approval by the institutional review board, electronic medical records were retrospectively reviewed and empyema criteria included: A positive pleural fluid culture or loculated pleural fluid collection on computed tomography or at the time of surgical exploration. This excludes patients with parapneumonic effusions that were culture negative or not treated clinically as an empyema. Inpatient management and documented MRSA nasal swab results were required for inclusion.

Data collection included patient demographics, MRSA colonization status, comorbidities, culture results, clinical management of empyema, and discharge disposition. Recent hospital admission was also captured, and defined as hospitalization within three mos prior to current admission. MRSA colonization status was considered positive if nasal swab culture on admission was positive for MRSA, or if the patient had a MRSA culture positive infection within the past year with no attempts at de-colonization (two patients); retesting was not performed. Methicillin-sensitive S. aureus (MSSA) colonized patients were analyzed with the cohort of patients with negative nasal swabs in order to analyze the effects of MRSA colonization specifically and in isolation. Charlson comorbity index (CCI) was calculated to compare severity of illness [16]. Pleural fluid cultures were obtained by sterile thoracentesis, at time of thoracostomy tube placement, or by operative culture. Organisms cultured from fluids aspirated during bronchoscopy were accepted if all other cultures were negative and greater than 100,000 colony-forming units of MRSA grew in culture. This accounted for 14.5% of positive cultures.

Pertinent secondary outcomes included surgical intervention, discharge disposition, and hospital length of stay. Clinical management options during the study period included thoracostomy tube with or without tube fibrinolysis. Surgical management consisted of medical thoracoscopy performed by an interventional pulmonologist, or surgical decortication via thoracoscopy or thoracotomy by a cardiothoracic surgeon. Medical thoracoscopy is a limited decortication procedure performed under conscious sedation using a semi-rigid medical pleuravideoscope with a working channel (Olympus, Tokyo, Japan). Surgical decortication is performed under general anesthesia and allows for complete drainage of the pleural space and total decortication of the lung. All treatment decisions were based upon the judgment of the consulting physician according to best practice and patient considerations. During this study period, there was no standard protocol for empyema management and not all patients underwent surgical consultation. None of the patients who underwent medical thoracoscopy were seen by a thoracic surgeon prior to that procedure.

The relationship between culture results and colonization status was evaluated using the Fisher exact test. Discharge disposition was dichotomized between home, and a skilled nursing facility, or a long-term care hospital, or death. Logistic regression was used to assess the relation between discharge disposition and the following potential covariates: MRSA colonization status, empyema culture results, gender, age, body mass index, CCI, management type, type of surgical intervention and recent hospital admission. Bivariate analysis was performed and all variables significant at 0.20 level were included in the final model. The validity of this model was assessed using the C-statistic and the Hosmer-Lemeshow goodness of fit test. Multicollinearity was assessed using the variance inflation factor.

Results

Culture results by colonization status

147 patients with empyema were identified; 16 (10.8%) were MRSA colonized. Demographics of each group are shown in Table 1. Colonized and non-colonized patients were of similar age and gender distribution. Colonized patients within our population were more likely to have recent hospitalization (63% vs. 29%, p=0.011) as well as carry a diagnosis of diabetes mellitus (38% vs. 15%, p=0.039). Only one patient in the study was admitted from a skilled nursing facility, and this patient was found to be MRSA colonized.

Table 1.

Patient Demographics

	Colonized (n=16)	Non-colonized (n=131)	p
Males	69% (11)	61% (80)	0.55
Mean age	50.1	43	0.23
Body Mass Index	29.2	24.9	0.12
Charlson Comorbidity Index	2.88	1.84	0.22
Diabetes mellitus	38% (6)	15% (20)	0.039
Recent antibiotic use	38% (6)	35% (46)	0.87
Recent hospitalization	63% (10)	29% (38)	0.011
MRSA infection	75% (12)	4.6% (6)	<0.001
Multi-organism	19% (3)^*	12% (16)^*	0.437
Negative culture	12.5% (2)	51.9% (69)	0.003

One multi-organism culture included MRSA in each group.

MRSA=Methicillin-resistant S. aureus.

Empyema cultures from MRSA-colonized patients had a substantially higher rate of MRSA positivity (75% vs. 4.6%; p<0.001). For all patients, the overall negative culture rate was 48% and multi-organism growth (with or without MRSA) was found in 13% of empyemas. Within the MRSA colonized group, a negative culture was much less likely (12.5% vs. 51.9%; p=0.003). A list of the most commonly isolated organisms by colonization status is given in Table 2. Interestingly, 10 (7.6%) of the non-MRSA colonized patients grew Candida albicans.

Table 2.

Most Frequently Isolated Organisms

	n	%
MRSA Colonized 16
MRSA	12	75.0
Klebsiella pneumoniae	3	18.8
Escherichia coli	2	12.5
Psuedomonas aeruginosa	1	6.3
Streptococcus pneumoniae	1	6.3
Negative culture	2	12.5
Non-MRSA Colonized 131
Candida albicans	10	7.6
MSSA	9	6.9
Coagulase negative Staphylococcus sp.	8	6.1
Streptococcus pneumoniae	8	6.1
MRSA	6	4.6
Streptococcus milleri	6	4.6
Enterococcus sp.	5	3.8
Negative culture	68	51.9

MRSA=Methicillin-resistant S. aureus; MSSA=Methicillin-sensitive S. aureus.

Patient outcomes by empyema culture results

The three empyema culture groups (MRSA culture positive, other culture positive, and culture negative empyema) were analyzed for length of stay, discharge disposition, and surgical intervention. Mean length of hospitalization for all patients with empyema was 16.6 days. The length of stay was shorter for culture-negative patients compared with MRSA positive culture or other positive culture (14.4 vs. 19.3 and 18.4 respectively; p=0.023) (Fig. 1). The following risk factors were associated with discharge to a skilled nursing facility or long-term care hospital: Higher CCI (0.78; 95% CI 0.62–0.98), and advanced age (0.96; 95% CI 0.93–0.98) (Table 3). The p value for the Hosmer-Lemeshow test is 0.594 and the C-statistic is 0.874. These indicate that the model is an adequate fit for the data. In addition, all variance inflation factors were less than 5, indicating that multicollinearity is not a problem in the model.

FIG. 1.

Length of stay in days.

Table 3.

Logistic Regression

Variable	OR	95% CI	p
MRSA colonization status	1.43	0.14–14.11	0.757
Empyema culture results	0.22	0.03–1.72	0.149
Age	0.96	0.93–0.98	0.002
BMI	0.99	0.92–1.08	0.965
CCI	0.78	0.62–0.98	0.035
Management type			0.977
Management type: Surgery vs tube	0.79	0.08–8.05
Management type: Surgery vs tube and surgery	0.80	0.10–6.48
Surgery type			0.133
Surgery type: Open vs no surgery	1.58	0.15–16.53
Surgery type: Minimally invasive vs no surgery	5.74	0.67–49.47
Recent hospital admission	0.81	0.29–2.21	0.676

MRSA=Methicillin-resistant S. aureus; BMI=body mass index; CCI=Charlson Comorbidity Index; OR=odds ratio; CI=confidence interval.

Within the entire study population, 59 patients (40.1%) were managed by tube thoracostomy alone, whereas the remaining 88 patients (59.9%) required surgical intervention. Of the 59 patients who did not undergo surgical decortication or medical thoracoscopy, only 18 were observed by a thoracic surgeon.

Only one-third of patients with MRSA empyema underwent surgical intervention, which is substantially less than the rate in the other two groups (33.3% vs. 61.0% of patients with positive culture other than MRSA and 65.7% for patients with culture negative empyema, p=0.043). Five of the 12 (41.7%) MRSA empyema patients managed with tube alone were deemed to be too ill for surgical management. One died in the hospital and the other four where discharged with empyema tubes. Ten of the 47 (21.3%) patients without MRSA empyema were deemed to be too ill for surgical management. Three died in the hospital, three were discharged with a chest tube, and four had the chest tube removed prior to discharge; p=0.26 between the MRSA and non-MRSA groups. Neither colonization nor MRSA culture positivity affected the type of surgical intervention required: Medical thoracoscopy, thoracoscopic surgery, or thoracotomy (Table 4).

Table 4.

Details of Management

	MRSA culture (n=18)	All other culture (n=129)	p
Management Types
Thoracostomy tube alone	12 (66.7%)	47 (36.4%)	0.0201
Surgery	6 (33.3%)	82 (63.6%)
Surgical Sub-Types
Medical thoracoscopy	2 (33.3%)	28 (34.1%)	1
Open decortication	2 (33.3%)	25 (30.5%)
Thoracoscopic decortication	2 (33.3%)	29 (35.4%)

MRSA=Methicillin-resistant S. aureus.

This study is underpowered for mortality, however, overall in-hospital mortality was 4.1% (six patients); 11.1% in MRSA empyema versus 3.1% in all other empyemas (p=0.158). Of the patients that died, two were culture positive for MRSA, two had negative cultures, one grew Escherichia coli, and one had polymicrobial culture (Enterobacter and MSSA).

Discussion

MRSA colonization is closely linked to MRSA-positive isolates from patients with empyema. Previous reports indicate that MRSA-colonized patients are generally more ill with greater number of comorbidities than non-colonized patients, which results in more frequent contact with the healthcare system resulting in MRSA colonization [2]. MRSA-colonized patients are more likely to have had recent hospitalization, long-term care facility admission, surgical ICU admission, or advanced age. These patients have greater number of comorbidities including congestive heart failure, chronic obstructive pulmonary disease, and diabetes mellitus [2]. Although the only statistically substantial difference in comorbidity between the colonized and non-colonized patients was the presence of diabetes mellitus, unexamined differences between the two patient populations may exist.

The MRSA empyema cohort had fewer patients who underwent surgical decortication. This may reflect that this population often has increased severity of illness that necessitates non-surgical management because of prohibitive surgical risk. Because of the small number of MRSA-positive empyema isolates, the data are underpowered to make any definitive conclusions on appropriate operative or non-operative management. This descriptive data does not support a definitive recommendation of surgical or non-surgical management in an otherwise fit patient.

Identification of a pathogen was more frequent in patients that were MRSA colonized, and this has been demonstrated previously for other infectious etiologies [11]. This may imply an inherent immuno-compromised state in MRSA colonized patients. Identification of the offending organism may be effected by initiation of antibiotics prior to obtaining a pleural fluid sample for culture. The overall negative culture rate of 48% and multi-organism growth of 13% is similar to the previously reported rates of 40% and 12% respectively [6]. Early empiric antibiotic administration was frequent at our institution and has been emphasized in accordance with the Surviving Sepsis Campaign [17]. Of patients with a positive culture, 81% received antibiotics prior to obtaining a culture, compared with 93% of patients who had negative cultures.

We recognize several limitations in this study. The lack of a consistent management at our institution makes it difficult to draw definitive conclusions regarding management strategies. Referral of patients with known or suspected empyema to medical pulmonologists or general thoracic surgeons is at the discretion of the primary team. Management during the study period was based on the admitting physician's best practice with no standard protocol being in place at our institution. Ten medical thoracoscopies were performed by an interventional pulmonologist without a trial of thoracostomy tube placement prior to the intervention. It is not possible to determine if these patients would have resolved with less aggressive therapy. The requirement for surgical intervention is affected by the stage of empyema and the time interval to diagnosis. Early stage empyema may resolve with tube thoracostomy alone. Eleven of the patients who did not undergo decortication were deemed medically inoperable without ever having been evaluated by a thoracic surgeon. The retrospective nature of the study and the limitations of the medical record preclude analysis of many important factors such as pulmonary function, consistent criteria for determining resolution of empyema, social support, performance status, timing of and rationale for antibiotic therapy. A prospective study with a defined treatment and imaging algorithm would be required to determine optimum treatment strategies.

The rate of fungal empyema in the non-MRSA group is high compared with previously published reports [18]. This might be the result of selection pressure from broad-spectrum antibiotic use. This was an unanticipated finding that lacks an adequate explanation.

Other reports that have demonstrated worse outcomes in the subset of patients with MRSA colonization [8,19]. Many of these patients became colonized through the healthcare system, and we must look further into means of prevention. MRSA colonization and its associated risk for development of MRSA infection have led to development of identification, isolation, and decolonization strategies [12,20 –24]. A large multicenter trial recently demonstrated decreased MRSA infection rates by performing universal decolonization of all ICU patients regardless of colonization status with intra-nasal mupirocin and daily bathing with chlorhexidine cloths [25].

Conclusion

MRSA-colonized patients hospitalized with empyema are highly likely to have MRSA culture positive empyema. MRSA-colonized patients with presumed empyema should be empirically started on antibiotics that cover MRSA, whereas other patients may not require the same spectrum of coverage while awaiting definitive culture results.

Footnotes

Acknowledgment

Presented at the 39th Western Thoracic Surgical Association Annual Meeting, Coeur d'Alene, Idaho, June 26–29, 2013.

Author Disclosure Statement

The authors have no conflicts of interest or sources of external funding to report.

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