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Are there studies that show or support the use of Ancef (cefazolin) 1 g daily for prophylaxis in patients with CSF leak?

Comment by InpharmD Researcher

No studies appear to report on the use of cefazolin (Ancef) 1 g daily for prophylaxis in patients with a CSF leak. Cefazolin 2-3 g have been studied in surgical settings where CSF leak occurred as a postoperative complication. A 2007 study reported using a perioperative cefazolin 1 g during endoscopic skull base surgery resulted in no infection in patients with postoperative CSF leak; however, another study found perioperative cefazolin 2 g did not reduce the rate of meningitis in patients with CSF leak following skull base surgery.

PubMed: csf leak cefazolin = 4 results; csf leak antibiotic prophylaxis = 23 results;



Background

A 2017 commentary mentions the Infectious Diseases Society of America (IDSA) recommends against prophylactic antimicrobial agents after basilar skull fracture and cerebrospinal fluid (CSF) leakage. This recommendation is based primarily on one randomized, single-center study with 109 patients. In this study, ceftriaxone 1 g BID was used, which is half the dosage recommended for meningitis treatment. Additionally, an unusually high rate of meningitis totally 20.1% ( 66% [8/12] if CSF leakage was present) was reported. This commentary challenges the IDSA recommendation against prophylactic antibiotic use in patients with CSF leak; however, the authors do not pose any correction or appropriate course of therapy. [1-2]

A 2015 Cochrane review and meta-analysis on the prevention of meningitis in patients with basilar skull fractures does not include any studies which used cefazolin. However, ceftriaxone 1 g dosed daily and BID have been studied. A subanalysis of 789 patients with documented CSF leakage showed a significant advantage from prophylactic antibiotics, with an odds ratio (OR) of 0.61 (95% confidence interval [CI] 0.37-0.99); however, the heterogeneity of antibiotics used in the nonrandomized studies makes it difficult to interpret these results. Due to the overall paucity of data, this meta-analysis was not able to support prophylactic antibiotic use in patients with basilar skull fractures, whether there is evidence of CSF leakage or not. [2-3]

References:

[1] Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 infectious diseases society of america’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis*. Clinical Infectious Diseases. 2017;64(6):e34-e65. doi:10.1093/cid/ciw861
[2] Kuehl R, Büchler A, Widmer AF, Battegay M. Digging out the evidence—how strong is the idsa recommendation against antibiotic prophylaxis in basilar skull fracture and cerebrospinal fluid leakage? Clinical Infectious Diseases. 2018;66(8):1319-1320. doi:10.1093/cid/cix984
[3] Ratilal BO, Costa J, Pappamikail L, Sampaio C. Antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures. Cochrane Database Syst Rev. 2015;(4):CD004884. Published 2015 Apr 28. doi:10.1002/14651858.CD004884.pub4

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Are there studies that show or support the use of Ancef (cefazolin) 1 g daily for prophylaxis in patients with CSF leak?

Please see Tables 1-2 for your response.


 

Role of Perioperative Antibiotics in Endoscopic Skull Base Surgery

Design

Retrospective, observational, database study

N= 90

Objective

To characterize the role of perioperative antibiotics in endoscopic endonasal skull base and pituitary surgery

Study Groups

Patients with intraoperative CSF leak (n=58)

Patients without intraoperative CSF leak (n=32)

Inclusion Criteria

Patients who had undergone endonasal skull base or pituitary surgery during the study period; were deemed to have adequate records

Exclusion Criteria

Incomplete data

Methods

This was a case series of 24-48 hours of single-agent perioperative antibiotics in patients who underwent endoscopic skull base surgery at a single tertiary-care center. Patient data was prospectively collected in a database that contained the office, hospital, and operative records of all patients that had undergone endoscopic skull base and pituitary surgery by the senior authors of this paper.

All of the patients underwent an endoscopic procedure and routinely received a single-agent IV antibiotic for 24 to 48 hours. Patients who had no known history of allergy received cefazolin 1 gram Q8H, while patients who had a known history of penicillin allergy received either vancomycin 1g Q12H or clindamycin 600mg IV Q8H. The choice between these two antibiotics was at the discretion of the surgeon.

The first dose of antibiotic was given at the time of induction with general anesthesia prior to the commencement of the procedure. Antibiotics were discontinued folowing nasal pack removal on postoperative day one or two. Once the patients were discharged, they underwent routine endoscopic examination and debridement of the sinonasal cavity.

Patients were then placed on gentamicin nasal spray (80 grams of gentamicin in 1 liter of normal saline) to start 2 weeks after surgery until the wound cavity was considered well healed, which was usually 2 to 3 months post-surgery. Those patients who were noted to have a clinical history and endoscopic findings consistent with sinusitis at follow-up received outpatient oral antibiotic therapy empirically in order to prevent more serious infections. 

Duration

Following discharge, patients were seen for an additional 2 to 3 months in order to ensure that their wound cavity had healed well. 

Outcome Measures

The main outcomes of this study were the occurrence of infectious complications and the need for additional antibiotics.

Baseline Characteristics

Baseline demographics were not discussed in this study.

Results

 

Intraoperative CSF leak

(n=58)

No intraoperative CSF leak

(n=32)

p-value

Histologic diagnosis

Secreting pituitary adenoma

Nonsecreting pituitary adenoma

Meningioma

Craniopharyngioma

Encephalocele

Other

 

12 (21%)

17 (29%)

7 (12%)

7 (12%)

8 (14%)

7 (12%)

 

19 (59%)

8 (25%)

0

1 (3%)

0

4 (12%)

 

0.01

NS

NS

NS

NS

NS

Cefazolin was used in 79 (88%) patients, vancomycin was used in 8 (8%) patients, and clindamycin was used in 3 (3%) patients. There no cases of meningitis or intracranial infections found in either group. Moreover, no antibiotic-related complications occured during the study. 

The differences between the two groups, in terms of their need for antibiotics during hospitalization or at follow-up, did not reach statistical significance. Additional antibiotics that were given during hospitalization were used in patients with a CSF leak to treat two (3%) patients with urinary tract infections, one (2%) patient with sinusitis, two (3%) patients for lumbar drain prophylaxis, one (2%) patient for postoperative fever, and one (2%) patient with aspiration pneumonia. Only one (3%) patient without CSF leak was given additional antibiotics in order to treat a case of sinusitis. 

Thirteen (22%) patients with a CSF leak and six (19%) patients without a CSF leak were given antibiotics during the first three months of follow-up in order to treat sinusitis or a nasal cavity infection. All of these infections were limited to the intranasal space and were successfully treated on an outpatient basis. 

Adverse Events

None reported

Study Author Conclusions

A single-agent antibiotic covering Gram-positive organisms for 24 to 48 hours may be adequate in anterior endoscopic skull base surgery to prevent serious CNS infectious complications.

InpharmD Researcher Critique

While researchers may not have found a significant difference in postoperative infectious outcomes between patients with and without intraoperative CSF leak, this could have been due to the fact they had a sample size of only 90 people. Furthermore, there was some heterogeneity between patients, tumor, and surgical variables that may have precluded identification of a specific indication for broad-spectrum antibiotics. 



References:

Brown SM, Anand VK, Tabaee A, Schwartz TH. Role of perioperative antibiotics in endoscopic skull base surgery. Laryngoscope. 2007;117(9):1528-1532. doi:10.1097/MLG.0b013e3180caa177

 

Antibiotic prophylaxis in endoscopic endonasal pituitary and skull base surgery

Design

Retrospective, cohort

N= 2,032

Objective

To assess the efficacy of our intraoperative antibiotic prophylaxis, analyzing the risk factors of postoperative meningitis

Inclusion Criteria

Patients who underwent endoscopic endonasal procedures at a single center in Italy; patients followed up for at least 30 days

Exclusion Criteria

Cases with preoperative suspicion of CSF infection

Methods

Each endoscopic endonasal procedure performed since 1998 in patients with no preoperative infections and a follow-up longer than 30 days were included in this study. The antibiotic protocol consisted of single antibiotic administration of ampicillin/sulbactam 3 g or cefazolin 2 g on induction. No postoperative antibiotics were administrated after 2005. All cases of CSF leak, meningitis, and systemic infection were recorded.

Duration

1998 to 2016

Baseline Characteristics

 

All patients (N= 2,032)

 

Age, years

50.1 ± 16.8  

Female

1,075 (52.9%)  

Results

 

Meningitis incidence

p-value

Intraoperative CSF Leak

Yes

No

 

12/666 (1.8%)

2/1366 (0.2%)

< 0.001

Postoperative CSF Leak 

Yes

No

 

7/69 (10.1%) 

7/1963 (0.4%)

< 0.001 

CSF Leak

Intraoperative only

Postoperative only

Intraoperative and Postoperative

 

6/449 (1.3%)

1/14 (7.1%)

6/45 (13.3%) 

< 0.001  

Intraoperative CSF leak occurred in 32.8% of the cases and postoperative CSF leak in 3.4%. The overall rate of meningitis was 0.69%.

Meningitis was statistically associated with intra- and post-operative CSF leak (p< 0.001). Other risk factors were the intradural extension of the tumors and their malignant histology. Extended approaches producing wide osteo-dural defects were also correlated with a higher risk of meningitis (p< 0.001)

Adverse Events

N/A

Study Author Conclusions

All surgical maneuvers to prevent, detect, and quickly repair intra- and postoperative CSF leak are crucial to avoid postoperative meningitis. The proposed prophylaxis protocol is comparable in safety to those recommended in literature as assessed by the low rate of meningitis.

InpharmD Researcher Critique

This study was not randomized and was retrospective. The retrospective design relies on proper documentation of healthcare providers, which some may have omitted certain information. Although the rate of meningitis is low and in line with others reported in the literature, the change of antibiotic prophylaxis protocol in 2005 might be considered a limitation of this study. 



References:

Milanese L, Zoli M, Sollini G, et al. Antibiotic Prophylaxis in Endoscopic Endonasal Pituitary and Skull Base Surgery. World Neurosurg. 2017;106:912-918. doi:10.1016/j.wneu.2017.07.075