Efficacy of Pre-Operative Nasal Staphylococcus aureus Screening and Chlorhexidine Chest Scrub in Decreasing the Incidence of Post-Resection Empyema

Abstract

Background:

We evaluated the efficacy of pre-operative Staphylococcus aureus (SA) screening and chlorhexidine chest scrub in decreasing the incidence of empyema after major pulmonary resections.

Methods:

For two years, a strategy aimed at decreasing post-resection empyema was instituted. This entailed pre-operative screening for nasal SA and chlorhexidine chest scrub the night before surgery (Group Swab-Scrub, n=192). Patients screened positive for SA, methicillin-resistant (MRSA) and methicillin-sensitive (MSSA), received 5 d of nasal mupirocin. Group Swab-Scrub was compared with patients two years earlier, who did not receive this pre-operative maneuver (Group Control, n=173). The extent of resection considered was lobectomy or greater. All patients received cefazolin (or clindamycin if allergic) prior to incision and 24 h postoperatively, except for patient in Group Swab-Scrub screening positive for MRSA, who received vancomycin. All patients had povidone-iodine skin preparation.

Results:

In Group Swab-Scrub, prevalence of nasal SA was 8.9% (17/192) two with MRSA and 15 with MSSA. There was no difference in patient demographics or operative characteristics between the Group Swab-Scrub and Group Control. There was also no difference in prolonged air-leak, empyema, wound infection, pneumonia, or mortality rates between the two groups. When stratifying for the extent of procedure, there was no difference in the incidence of empyema after lobectomy (Group Swab-Scrub, 3.9% [7/177] versus Group Control, 2.0% [3/151]; p=0.352) or pneumonectomy (Group Swab-Scrub, 6.7% [1/15] versus Group Control, 13.6% [3/22]; p=0.633). In both univariate and multivariable analysis, prolonged air-leak and pneumonectomy were significant risk factors for empyema.

Conclusions:

Preoperative screening for nasal SA and chlorhexidine chest scrub does not seem to decrease empyema rates after major pulmonary resection. Prolonged air-leak and pneumonectomy continue to be significant risk factors for developing empyema. The number of patients undergoing pneumonectomy in this study is small and further studies are needed for this patient population.

The reported incidence of empyema in large series of patients undergoing major pulmonary resection ranges from 1% to 5% [1 –3]. The rate of empyema is highest after pneumonectomy, with a reported incidence of up to 16% [4]. Empyema after pulmonary resection results in substantial patient morbidity and financial cost to the heath care system. In cardiac surgery, strategies involving screening for nasal SA, mupirocin eradication along with pre-operative chlorhexidine chest scrub has been shown by many authors to decrease the incidence of surgical site infection (SSI) [5 –10]. However, there is little data in the literature to evaluate the efficacy of these tactics in the thoracic patient undergoing pulmonary resection. In this study, we determined if screening for nasal SA, mupirocin therapy for those screened positive, and pre-operative chlorhexidine chest scrub could decrease the incidence of empyema after major pulmonary resection.

Patients and Methods

During a 2-y period, our institution implemented a policy to decrease the incidence of SSI. This strategy involved screening for nasal SA, mupirocin eradication, and pre-operative chlorhexidine scrub. Screening for SA was performed by nasal swab culture one week prior to surgery at the time of pre-admission testing. Patients screened positive for SA, methicillin-resistant SA (MRSA) or methicillin-sensitive SA (MSSA), were treated with 5 d of 2% mupirocin applied to each nostril twice a day. Re-screening for nasal SA after treatment was not routinely performed. For pre-operative chest scrub, the hemi-thorax was scrubbed the night before surgery with a 4% chlorhexidine surgical scrub sponge. The patients undergoing this scrub (Group Swab-Scrub) were compared with patients 2 y prior who did not have SA screening, mupirocin therapy, nor pre-operative chlorhexidine chest scrub (Group Control). Patients in both groups received cefazolin (clindamycin if allergic) within 1 h prior to incision and 24 h postoperatively; however, patients in Group Swab-Scrub screening positive for MRSA received vancomycin also within 1 h prior to incision and 24 h postoperatively. All patients had povidone-iodine skin preparation for surgery. During the earlier time period of this trial, our institution routinely used povidone-iodine for skin preparation as data regarding chlorhexidine were just emerging. We continued the use of povidone-iodine for all patients in this study in order to keep the skin preparation similar between the groups. Only patients undergoing elective major pulmonary resection (lobectomy or greater) were evaluated. Our primary outcome was the incidence of empyema. Secondary outcomes included pneumonia and surgical site infection (any of empyema, surgical site infection, or pneumonia). Empyema was defined as the presence of purulent pleural fluid or pleural fluid that cultured positive. Surgical site infection was defined as an incision with erythema, an incision with drainage, or an incision that required opening. Pneumonia was defined as the presence of any two clinical features of hypoxia, chest radiograph infiltrate, fever, or productive sputum. Mortality was defined as death in-hospital or within 30 days of surgery. Staging for patients with non-small cell lung cancer was according to the American Joint Committee on Cancer, 6th edition [11].

Data were derived from a prospective thoracic surgery database. All procedures were performed by a single surgeon (TN). The Shapiro-Wilk test was used to test for normal distribution of continuous data. Continuous variables were reported as mean±standard deviation and compared using Student t or Mann-Whitney U test. Categorical variables were reported as counts with the corresponding proportion and compared using χ² or the Fisher exact test. Multiple logistic regression analysis was used to identify independent risk factors for empyema, entering variables with p<0.10 found at univariate analysis. All tests were two-tailed with p<0.05 considered to be statistically significant. The software SPSS 17.0 for Windows (SPSS Inc., Chicago, IL) was used for data analysis. Our Institutional Review Board approved this study and waived consent as this study was a retrospective review of data from our prospective database, the scrub of Group Swab-Scrub was implemented by our institution as a quality improvement measure, and the treatment received by all patients represented the standard of care.

Results

The study population included 365 patients, with 188 (51.5%) being male. Median age was 67 years (mean, 66.5 years), with a range of 21 to 90 years. The most common indication for major pulmonary resection was non–small cell lung cancer, seen in 341 (93.4%) patients. Mortality occurred in six (1.6%) patients, due to pneumonia in three patients, pulmonary edema in two patients, and pulmonary embolism in one patient. Empyema occurred in 14 (3.8%) patients, four patients after pneumonectomy and 10 patients after lobectomy—all in absence of bronchopleural fistula. Treatment for the four patients with empyema after pneumonectomy involved thoracoscopic debridement followed by post-operative antibiotic irrigation as described by Ng et al [12]. Treatment for the 10 patients with empyema after lobectomy involved tube thoracostomy in four patients, thoracotomy for decortication in three patients, tube thoracostomy with thrombolytic therapy in two patients, and rib resection along with wound vacuum-assisted closure device in one patient. In Group Swab-Scrub, 17 patients (8.9%) screened positive for nasal SA, two patients (1.0%) for MRSA (both without complication of empyema), and 15 patients (7.8%) for MSSA (one with MRSA empyema and one with MSSA empyema). There was no adverse reaction to nasal mupirocin or chlorhexidine chest scrub.

Comparison of patient demographics between Group Swab-Scrub and Group Control is shown in Table 1, with no difference found between the groups. Comparison of intra-operative and post-operative characteristics between the two groups is shown in Table 2. Group Control had a higher proportion of patients receiving red blood cell concentrate transfusion (one unit or more during hospital admission); otherwise there was no significant difference between two groups.

Table 1.

Patient Demographics

Characteristic	Group Control (n=173)	Group Swab-Scrub (n=192)	p
Age (years)	66.3±10.7	66.7±11.2	0.766
Male	93 (53.8%)	95 (49.5%)	0.414
BMI	26.28±5.11	26.92±4.63	0.350
FEV₁	2.02±0.68	2.07±0.67	0.445
% predicted FEV₁ (%)	77.18±21.35	80.52±19.35	0.118
% predicted DLCO (%)	76.44±21.56	75.56±21.41	0.713
ASA Class 2	47 (28%)	63 (33.5%)	0.438
3	113 (67.3%)	119 (63.3%)
4	8 (4.8%)	6 (3.2%)
Neoadjuvant Therapy^†	12 (6.9%)	9 (4.7%)	0.357
Non-neoplastic indications	9 (5.2%)	7 (3.6%)	0.468
Non-small cell cancer^*
Stage I	98 (61.3%)	126 (69.6%)	0.256
Stage II	27 (16.9%)	30 (16.6%)
Stage III	32 (20%)	23 (12.7%)
Stage IV	3 (1.9%)	2 (1.1%)

†

Concurrent chemotherapy and 5040 cGy radiation; ^*AJCC 6th edition.

BMI, body mass index; FEV₁, forced expiratory volume in 1 sec; DLCO, diffusion capacity of lung for carbon monoxide; ASA, American Society of Anesthesiologists.

Table 2.

Intra-Operative and Post-Operative Characteristics

Characteristic	Group Control (n=173)	Group Swab-Scrub (n=192)	p
Estimated blood loss (mL)	340.61±393.74	283.72±326.53	0.103
Operative time (min)	142.2±51.4	132.0±43.4	0.071
Sleeve lobectomy	5 (2.9%)	1 ( 0.5%)	0.105
Pneumonectomy	22 (12.7%)	15 ( 7.8%)	0.121
Chest wall prosthesis	4 (2.3 %)	2 ( 1.0%)	0.428
Packed red cell transfusion	53 (30.6%)	38 (19.8%)	0.017
Mortality^†	4 (2.31%)	2 ( 1.04%)	0.428
Prolonged air leak^§	14 (8.09%)	8 ( 4.17%)	0.116
Pneumonia	7 (4.0%)	6 ( 3.13%)	0.635
Empyema	6 (3.47%)	8 ( 4.17%)	0.729
Wound infection	1 (0.58%)	1 ( 0.52%)	1.000
Surgical site infection^*	13 (7.51%)	15 ( 7.81%)	0.904
Days with chest tube	5.20±5.58	5.08±3.52	0.120

†

Death in-hospital or 30 days after surgery.

Air leak greater than 7 d.

Any of pneumonia, empyema or wound infection.

For the primary outcome, there was no difference in the rate of empyema (all-cause, due to SA, or due to MRSA) between Group Control and Group Swab-Scrub (Table 2). Stratifying for the extent of procedure, there was no difference between the two groups in the rate of empyema after lobectomy (Group Control, 2.0% [3/151] versus Group Swab-Scrub, 3.9% [7/177]; p=0.352) and after pneumonectomy (Group Control, 13.6% [3/22] versus Group Swab-Scrub, 6.7% [1/15]; p=0.633). For the secondary outcomes, there was no difference between the two groups in the incidence of wound infection, pneumonia, or surgical site infection (Table 2).

Univariate analysis of risk factors for developing empyema after major pulmonary resection is shown in Table 3. After analysis, only pneumonectomy and prolonged air leak remained independent risk factors for developing empyema after major pulmonary resection (Table 4).

Table 3.

Risk Factors for Empyema, Uni-Variate Analysis

Characteristic	No empyema (n=351)	Empyema (n=14)	p
Age (years)	66.38±11.02	70.07±9.03	0.229
Male	178 (50.71%)	10 (71.43%)	0.128
BMI	26.60±4.89	26.79±4.29	0.930
FEV₁	2.05±0.68	1.91±0.58	0.507
% predicted FEV₁ (%)	79.20±20.44	72.08±17.22	0.216
% predicted DLCO (%)	76.27±21.50	67.58±19.03	0.169
ASA Class 2	108 (31.4%)	2 (16.7%)	0.447
3	223 (64.8)	9 (75%)
4	13 (3.8%)	1 (8.3%)
Neoadjuvant Therapy^†	21 (5.98%)	0	1.000
Non small cell^§ Stage I	219 (66.77%)	5 (38.46%)	0.033
Stage II	51 (15.5%)	6 (46.2%)
Stage III	53 (16.16%)	2 (15.38%)
Stage IV	5 (1.52%)	0
Non-neoplastic indications	15 (4.27%)	1 (7.14%)	0.472
Group Swab-Scrub	184 (52.4%)	8 (57.1%)	0.729
Estimated blood loss (mL)	307.83±360.84	383.93±361.44	0.455
Operative time (min)	136.88±46.95	135.07±62.37	0.945
Packed red cell transfusion	84 (23.93%)	7 (50.00%)	0.051
Sleeve lobectomy	6 (1.71%)	0	1.000
Pneumonectomy	33 (9.40%)	4 (28.57%)	0.043
Chest wall prosthesis	5 (1.42%)	1 (7.14%)	0.210
Prolonged air leak^*	19 (5.41%)	3 (21.43%)	0.045
Pneumonia	12 (3.42%)	1 (7.14%)	0.404
Wound Infection	2 (0.57%)	0	1.000
Days with chest tube	4.99±4.32	8.86±8.73	0.282

†

Concurrent chemotherapy and 5040 cGy radiation.

AJCC 6th edition.

Air leak greater than 7 d.

BMI, body mass index; FEV₁, forced expiratory volume in 1 second; DLCO, diffusion capacity of lung for carbon monoxide; ASA, American Society of Anesthesiologists.

Table 4.

Risk Factors for Empyema, Multi-Variable Analysis

Characteristic	Odds Ratio	95% confidence Interval	p
Stage (non-small cell cancer)	1.04	0.48–2.21	0.930
Packed red cell transfusion	2.31	0.72–7.40	0.160
Pneumonectomy	4.81	1.07–21.74	0.041
Prolonged air leak^*	7.82	1.78–34.33	0.006

Air leak greater than 7 d.

Discussion

The majority of sternal surgical site infection after cardiac surgery are cultured positive for SA [8]. Using DNA fingerprinting by pulsed field gel electrophoresis, studies by Jakob et al. [13] and Bode et al. [14] have shown the source of SA to be from the patients' nares. Furthermore, studies by Jakob et al. [13], San Juan et al. [15] and Kluytmans et al. [16] have all shown nasal colonization with SA to be an independent risk factor for sternal surgical site infection after cardiac surgery. The prevalence of nasal SA amongst cardiac surgical patients is reported to be 20% [6,8,13], with the prevalence of nasal MRSA at 2% [9,10]. These data would suggest that identifying and eradicating nasal SA would decrease the incidence of postoperative SSI; however, results of randomized studies on this subject have been conflicting.

Randomized trials showing no benefit to SA screening and eradication were published by Suzuki et al. [17] in 2003 (general surgical patients) and Konvalinka et al. [18] in 2006 (cardiac surgical patients), whereas randomized trials showing benefit were published by Perl et al. [19] in 2002 (all surgical patients) and Bode et al. [14] in 2010 (all surgical patients). Three of these four randomized trials combined pre-operative chlorhexidine chest scrub with nasal SA screening and mupirocin therapy [14,17,18]. Although two of the four randomized trials were negative, the strength lies within the two positive trials. Negative trials by Suzuki et al. [17] and Konvalinka et al. [18] randomized only a small number of patients (397 and 257, respectively), whereas the two positive trials by Perl et al. [19] and Bode et al. [14] randomized a much larger number of patients (3,864 and 917, respectively). Furthermore, the negative trial by Konvalinka et al. [18] has been criticized for the 46.5% eradication rate of nasal SA prior to surgery in the placebo group. This could be explained by the trial site, Ontario, Canada, where nasal mupirocin could be purchased without a prescription during the study period, thus raising questions regarding compliance to the trial's placebo arm. Meta-analysis of both randomized and non-randomized trials have favored SA screening and mupirocin treatment. Systematic reviews by Kallen et al. [20] and van Rijen et al. [21] have shown significant decreases in the incidence of SSI (non-general surgical procedures) and post-operative SA nosocomial infection respectively. As mentioned in the introduction, the vast majority of published studies in cardiac surgery are in favor of SA screening and eradication [5 -10]. Although there are many studies in cardiac surgical literature, little data has been published to evaluate the effectiveness of such strategies in decreasing the incidence of SSI in non-cardiac thoracic surgery.

Our data would indicate that SA screening, mupirocin therapy, and pre-operative chlorhexidine chest scrub does not decrease the incidence of empyema after major pulmonary resection. Due to the low prevalence of nasal SA colonization (8.9%) and the low incidence of post-resection empyema (3.8%) seen in our study, it may be difficult to show benefit for any given intervention. However, every surgeon should evaluate the prevalence of nasal SA and the incidence of empyema at their own institution as this strategy may benefit those institutions with high rates. The risk factors for empyema found in our study (blood transfusion by uni-variate analysis, pneumonectomy and prolonged air leak by multi-variable analysis) are consistent with the published literature [4,22].

Our study has several limitations. First, the number of patients in our study is small, which is a possible reason why we did not find a statistically significant difference in the rates of post-pneumonectomy empyema. Second, this is retrospective study, and although the two groups were similar (Table 1 and Table 2), hidden confounding factors can still exist that only a randomized study can control for. Third, the two groups of patients underwent surgical procedure during consecutive periods rather than in a randomized fashion. Therefore, it is possible that our data were biased by surgical experience, which is gained over time. Fourth, our study depended on patient compliance with nasal mupirocin therapy and chlorhexidine chest scrub. We could not ensure 100% compliance with treatment for all patients in Group Swab-Scrub. Finally, our trial involved using nasal mupirocin selectively—that is, only for those patients screened positive for SA in Group Swab-Scrub. Therefore, it is not known whether treating all the patients in Group Swab-Scrub (instead of selectively treating) would have resulted in a different outcome, namely a positive study. However, there are many positive trials with the selective use of nasal mupirocin [7 –9,14,21] and non-selective use may result in the development of mupirocin-resistant and methicillin-resistant strains of SA [23,24].

In conclusion, prolonged air leak and pneumonectomy are independent risk factors for the development of empyema after pulmonary resection. A strategy that consists of screening for nasal SA, mupirocin therapy for patients screening positive, and pre-operative chlorhexidine chest scrub does not decrease the incidence of empyema after major pulmonary resection. Further studies are warranted in patients undergoing pneumonectomy using a larger sample size and including comparisons of more clinical outcomes such as hospital days and treatment costs.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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