Analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach.

The aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. Bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. The sensitivity of these bacteria to cephalosporin, a representative prophylactic antibiotic, was examined. Staphylococcus epidermidis was the most frequently detected species in both spaces; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus. In contrast, Corynebacterium species were found mainly in the nasal cavity, and anaerobic bacteria were found only in the sphenoid sinus. Bacteria that were resistant to cephalosporin were found in the nasal cavity in 3.2% of patients and in the sphenoid sinus in 20% of patients. In conclusion, the composition of bacterial flora, including bacteria that are resistant to prophylactic antibiotics, differs between the nasal cavity and the sphenoid sinus.

Introduction

The endoscopic endonasal transsphenoidal approach (EEA) has recently become the preferred surgical technique for lesions in the sellar and clival regions, including pituitary adenomas,[1)] Rathke's cysts,[2)] craniopharyngiomas,[3)] and chordomas.[4)] Although EEA is safe with low morbidity and mortality, it is a “clean-contaminated” procedure. Therefore, steps must be taken to prevent postoperative infections such as meningitis and sinusitis. However, the protocol for antibiotic prophylaxis has not been clarified in the context of EEA. In fact, only a few papers on this topic have been published in recent years, and they largely refer to patients undergoing conventional transsphenoidal surgery.[5–7)] According to these reports, the rates of meningitis and sinusitis after transsphenoidal surgery range from 0.5% to 14% and from 3.6% to 9.6%, respectively. Postoperative meningitis is one of the most critical complications of EEA, especially in procedures involving the subdural space. Orlando et al. retrospectively evaluated the rate of postsurgical infection in 170 patients who underwent EEA and showed that a third-generation cephalosporin was an appropriate prophylactic antibiotic.[8)] In this study, we analyzed the bacterial flora of the preoperative nasal cavity and the intraoperative sphenoid sinus mucosa in patients undergoing EEA, and we discuss the use of prophylactic antibiotics in such patients.

Materials and Methods

The research ethics board of Keio University Hospital approved the study without the need to obtain written informed consent from patients.

Bacterial cultures of the preoperative nasal cavity and the intraoperative sphenoid sinus mucosa were established for 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent EEA between May 2011 and May 2013 in the Department of Neuro-surgery, Keio University Graduate School of Medicine. Nasal swabs was obtained before surgery, and mucosa of the sphenoid sinus was taken for culture after opening the anterior wall of the sphenoid sinus during surgery. The composition of the bacterial flora and the rates of sensitivity to cephalosporins were compared between the anatomical spaces. The most common reason for a transsphenoidal operation was a pituitary adenoma (72.5%) followed by a Rathke's cyst (10%), chordoma (7.5%), meningioma (5%), cholesterol granuloma (2.5%), and giant cell tumor (2.5%) (Table 1). Twelve patients (30%) developed major intraoperative cerebrospinal fluid (CSF) leakage, and two patients (5%) developed postoperative CSF leakage that required reoperation. A subdural procedure was performed in two patients (5%). Postoperative meningitis or sinusitis did not occur in any patient in this series. Administration of antibiotics was based on the amount of intraoperative CSF leakage; in cases with a large amount of CSF leakage (subdural procedure and wide fenestration of the diaphragm, in which subdural structures were visible), a third-generation cephalosporin was administered for prophylaxis of postoperative meningitis, and in cases with little or no CSF leakage (minor fenestration of the diaphragm, in which subdural structures were not visible), a first- or second-generation cephalosporin was selected. Antibiotics were administered for at least 2 days after operation; the administration of antibiotics was extended up to 1 week depending on the amount of intraoperative CSF leakage. Intensive irrigation with saline was performed in all surgeries.

Table 1

Clinical features of 40 patients who underwent endoscopic transsphenoidal surgery

Sex
Male (n)	20
Female (n)	20
Age
Average (y)	52.2
Range (y)	15–77
Disease
Pituitary adenoma	29
Rathke's cyst	4
Chordoma	3
Meningioma	2
Cholesterol granuloma	1
Giant cell tumor	1
Total patients (n)	40

Results

The species composition of the preoperative nasal cavity cultures and the intraoperative sphenoid sinus cultures is shown in Table 2. The most frequently detected species in both spaces was Staphylococcus epidermidis; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus.

Table 2

Distribution of microorganisms in cultures of the preoperative nasal cavity and the intraoperative sphenoid sinus

Microorganisms	Nasal cavity culture			Sphenoid sinus culture
	Total number (n)	First-generation cephalosporin resistance (n)	Third-generation cephalosporin resistance (n)	Total number (n)	First-generation cephalosporin resistance (n)	Third-generation cephalosporin resistance (n)
Staphylococcus epidermidis	24	1	1	26	12	4
S. aureus	10	0	0	3	0	0
Staphylococcus spp.	4	0	0	3	0	0
S. lugdunensis	0	0	0	1	1	0
Gamma streptococcus	0	0	0	2	0	0
Alpha-streptococcus	3	0	0	3	0	0
Aerobic G-pos. cocci,	5	0	0	0	0	0
Propionibacterium acnes	0	0	0	12	0	0
Propionibacterium spp.	0	0	0	12	0	0
Anaerobic G-pos. cocci	0	0	0	2	0	0
Anaerobic G-pos. rods	0	0	0	1	0	0
Corynebacterium spp.	12	0	0	3	0	0
Klebsiella oxytoca	1	0	0	1	0	0
Enterobacteraero genes	1	1	0	1	1	0
Haemophilus influenzae	1	0	0	0	0	0
Moraxella spp.	1	0	0	0	0	0
Branhamella catarrhalis	2	0	0	0	0	0
Total	62	2 (3.2%)	1 (1.6%)	70	14 (20%)	4 (5.7%)

In the nasal cavity cultures, Staphylococcus and Corynebacterium species were found most frequently. Among the 62 isolates detected in nasal cavity cultures, two (3.2%) were resistant to cephalosporins (S. epidermidis and Enterobacter aerogenes). Three patients (7.5%) had no bacteria in the nasal cavity.

In the sphenoid sinus cultures, anaerobic bacteria were found in addition to Staphylococcus species. More isolates were resistant to cephalosporins in the sphenoid sinus cultures (20%) than in the nasal cavity cultures (3.2%). Furthermore, the percentage of isolates in the sphenoid sinus cultures that were resistant to first-generation cephalosporins (20%) was higher than that of those resistant to third-generation cephalosporins (5.7%). Two out of 40 patients (5%) had no bacteria in the sphenoid sinus. Three of 12 cases with intraoperative CSF leakage had S. epidermidis that was resistant to cephalosporins. An additional 13 cases had minor CSF leakage.

In six patients, the species composition of the nasal cavity culture was identical to that of the sphenoid sinus culture. In all six cases, the species composition included S. epidermidis. Fifteen patients had no species in common between the nasal cavity and sphenoid sinus cultures. Among the remaining 19 patients, 17 had cultures that contained Staphylococcus species, and in 16 cases these species included S. epidermidis (Table 3).

Table 3

Contents of bacteria in each case

Case No.	Nasal cavity	Sphenoid sinus
1	Staphylococcus epidermidis	S. epidermidis
2	S. epidermidis	S. epidermidis
3	S. epidermidis	S. epidermidis*
4	S. epidermidis	S. epidermidis* **
5	S. epidermidis* **	S. epidermidis* **
6	S. epidermidis, Alpha-streptococcus, K. oxytoca	S. epidermidis, Alpha-streptococcus, K. oxytoca
7	S. epidermidis	S. epidermidis*, Propionibacterium spp.
8	S. epidermidis	S. epidermidis*, Propionibacterium spp.
9	S. epidermidis	S. epidermidis, Propionibacterium spp.
10	S. epidermidis	S. epidermidis*, P. acnes, Propionibacterium spp., Alpha-hemo. streptococcus
11	S. epidermidis	S. epidermidis, Prevotella spp.
12	S. epidermidis, S. aureus	S. epidermidis
13	S. epidermidis, S. aureus	S. epidermidis, Anaerobic G-pos. rods,
		Propionibacterium spp.
14	S. epidermidis, S. aureus, Haemophilus influenzae, Moraxella spp.	S. epidermidis, S. aureus, P. acnes, Alpha-hemo. streptococcus, Gamma-hemo. Streptococcus
15	S. epidermidis, Corynebacterium spp.	S. epidermidis, Propionibacterium spp.
16	S. epidermidis, Corynebacterium spp.	S. epidermidis*, Propionibacterium spp.
17	S. epidermidis, Corynebacterium spp.	S. epidermidis*, Propionibacterium spp., Gamma-hemo streptococcus
18	Staphylococcus spp.	S. epidermidis, P. acnes
19	Staphylococcus spp.	S. epidermidis, P. acnes
20	Staphylococcus spp., S. aureus, Corynebacterium spp., Aerobic G-pos. cocci, B. catarrhalis	S. epidermidis, Propionibacterium spp.
21	S. epidermidis, S. aureus, Corynebacterium spp.	Staphylococcus spp., Propionibacterium spp.
22	S. epidermidis, Corynebacterium spp.	Staphylococcus spp., Enterobacter aerogenes*, P. acnes
23	Staphylococcus spp., S. epidermidis	S. aureus, S. lugdunensis*
24	S. epidermidis, Corynebacterium spp., Aerobic G-pos.	Corynebacterium spp., P. acnes
	cocci
25	Aerobic G-pos. cocci, Alpha-hemo. streptococcus	S. epidermidis* **, Aerobic G-pos. cocci
26	Staphylococcus spp., S. aureus, Alpha-hemo	Anaerobic G-pos. rods, Anaerobic G-pos. cocci
	streptococcus
27	Staphylococcus spp., enterobacteraerogenes*	Negative
28	S. epidermidis, S. aureus, Corynebacterium spp.	Propionibacterium spp.
29	S. epidermidis, S. aureus	Propionibacterium spp., Corynebacterium spp.
30	S. epidermidis, Corynebacterium spp., B. catarrhalis	P. acnes
31	S. aureus	S. epidermidis
32	S. aureus, Aerobic G-pos. cocci	Corynebacterium spp.
33	Corynebacterium spp.	Staphylococcus spp., Propionibacterium spp.
34	Corynebacterium spp.	S. epidermidis* **
35	Corynebacterium spp., Aerobic G-pos, cocci, B. catarrhalis	Negative
36	Negative	S. epidermidis
37	Negative	S. epidermidis*, Propionibacterium spp.
38	Negative	S. epidermidis*, P. acnes
39	Negative	S. aureus, P. acnes
40	Negative	P. acnes

1–6: completely matched, 7–25: partially matched, 25–40: not matched, *: resistant to first-generation cephalosporin, **: resistant to third-generation cephalosporin.

Discussion

EEA should be considered a procedure that exposes at-risk patients to infectious complications including meningitis and sinusitis. The risk of meningitis is reported to be associated with the incidence of CSF leakage and its incidence ranges from 0.5% to 14%, as reported in the literature.[6,9–14)] On the other hand, the rate of the sinusitis ranges from 3.6% to 9.6%.[7)] Prophylaxis of postoperative infections is important, and we present the first report of the species composition and antibiotic sensitivity of bacteria in the endonasal transsphenoidal corridor.

Preoperative nasal cavity culture is meaningless for prediction of the bacteria of the sphenoid sinus. This study showed that the bacterial species composition often differed between the nasal cavity and the sphenoid sinus. This suggests that prophylactic use of antibiotics may be problematic when based on results from preoperative nasal cavity cultures. The environments of the two anatomical spaces differ. Whereas drug-resistant bacteria readily drain from the open nasal cavity, resistant bacteria are easily stored in the nearly closed sphenoid sinus. Therefore, if infections such as meningitis persist despite the administration of third-generation cephalosporins, results from intraoperative sphenoid sinus cultures need to be considered when selecting antibiotics.

The choice of prophylactic antibiotic usually depends on the pharmacokinetic profile of the drug and the local bacterial flora.[8)] Cephalosporins tend to be administered to prevent postoperative meningitis.[15)] Orland et al. described the usefulness of a third-generation cephalosporin as a prophylactic antibiotic.[8)] Third-generation cephalosporins reach the levels in the CSF that are sufficient to inhibit Staphylococcus species and gram-negative bacilli,[16)] and they are useful for reducing the risk of meningitis. In this study, bacteria that were sensitive to cephalosporins represented 96.8% of the isolates in the nasal cavity and 80% of those in the sphenoid sinus. Furthermore, in the sphenoid sinus, the percentage of isolates that were resistant to first-generation cephalosporins (20%) was higher than the percentage of isolates that were resistant to third-generation cephalosporins (5.7%). Considering these facts, third-generation cephalosporins should be recommended for preventing postoperative infections, especially when subdural procedures are performed. In fact, Orland et al. applied a prophylactic antibiotic regimen including a third-generation cephalosporin and found low incidences of meningitis (0.58%) and sinusitis (1.17%).[8)] Despite the existence of bacteria resistant to third-generation cephalosporins, no meningitis occurred in our series. We believe that intensive irrigation with saline, in addition to postoperative antibiotics, may be effective for preventing postoperative meningitis.[17)] Considering the prevalence of resistant bacteria, intraoperative washing of the nasal cavity and the sphenoid sinus before cutting of the dura is recommended.

Conclusion

Bacterial flora differs between the nasal cavity and the sphenoid sinus. Therefore, the use of preoperative nasal cavity cultures as the basis for selecting the correct antibiotic for prevention of meningitis is problematic. Third-generation cephalosporins are a reasonable choice for preventing meningitis after EEA. Intraoperative irrigation should be performed because of the existence of third-generation cephalosporin-resistant bacteria in the sphenoid sinus.