Is there any benefit to using cefazolin or vancomycin in surgical irrigation for an incision and drainage of an infected joint (not for prevention of SSI)?

Comment by InpharmD Researcher

Available literature evaluating antibiotic irrigation containing cefazolin or vancomycin is primarily limited to the prevention of surgical site infections. One retrospective study reported the benefits of vancomycin powder along with povidone-Iodine irrigation in improving the success rates of irrigation and debridement with modular component and liner exchange for periprosthetic joint infection. Though cefazolin irrigation has been shown to achieve protective cefazolin concentrations in the wound, which lasts longer compared to intravenous administration, the clinical applicability in the setting of infected joints requires further evaluation.

cefazolin irrigation incision drainage= 5 results (1 relevant); vancomycin irrigation incision drainage= 10 results (0 relevant); debridement and antibiotic irrigation lavage infected joint treatment (filter: clinical trial)= 7 results (0 relevant)

Background

A recently published review describing irrigation solutions and antibiotic powders in primary and revision total joint arthroplasty notes that irrigation solutions are commonly used in cases of established periprosthetic joint infection to assist in the removal of the infecting organism, and the ideal agent should have minimal cytotoxicity and be safe to use in the normal tissue but be effective against the infecting organism. The review primarily focuses on use of irrigation solutions, including betadine, chlorhexidine, hydrogen peroxide, and acetic acid, and does not describe use of individual antibiotic agents within irrigation solutions, such as cefazolin or vancomycin. However, use of vancomycin powder is described to produce a high local concentration of the antibiotic that would not be attainable with intravenous administration without creating systemic toxicity. Some studies have looked at vancomycin powder and povidone-iodine combination for the treatment of prosthetic joint infection and found promising findings. However, ongoing research is being conducted to further look at benefits. [1]

A 2019 literature review on the use of irrigation fluids for treatment of orthopedic infections discussed the addition of antibiotics to surgical irrigation. In general, antibiotics should not be added to intrawound irrigation with a grade A level recommendation, with strong clinical evidence showing no benefit. With various antibiotics, mechanisms of action and longer half-life contribute to a limited or negligible effect when applied during irrigation. However, this is not applicable to the use of topical antibiotics or powdered formulations placed into surgical wounds before closure. The review did not further elaborate on the use of topical antibiotics, such as cefazolin or vancomycin, during incision and drainage of infected joints. [2]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

For Total Hip/Total knee/Hip Hemiarthroplasty cases, are there any antimicrobial irrigations used in the past with Gram-Positive coverage?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-3 for your response.

Vancomycin Povidone-Iodine Protocol Improves Survivorship of Periprosthetic Joint Infection Treated With Irrigation and Debridement
Design	Single-center, retrospective study N= 73
Objective	To examine the patients who received irrigation and debridement with modular component and liner exchange (IDLE) in order to compare infection-free prosthetic status between patients who received vancomycin povidone-iodine (VIP) and those who did not.
Study Groups	VIP (n= 36) Control (n= 37)
Inclusion Criteria	Patients treated with irrigation and debridement with modular component and liner exchange (IDLE) and VIP protocol
Exclusion Criteria	Patients with chronic cases, hematoma, and wound complications, documented iodine allergy
Methods	The patient population consisted of the VIP group which received a dilute 0.35% povidone-iodine lavage followed by vancomycin powder 1 g placed into the deep and superficial fascia; and a control group that received standard irrigation and debridement with modular component and linear exchange (IDLE). Both groups received systemic antibiotics prior to surgery. Patients were evaluated after the surgery at regular intervals. (2-3-weeks, 6-weeks, 3-months, 12-months, and yearly).
Duration	Data collection period: March 2014 to January 2016 Mean duration of follow up: 27.1 ± 7.8 months
Outcome Measures	Primary outcome: failure (defined as requiring surgical intervention for infection, persistent fistula/drainage/joint pain at last follow-up visit, death related to joint infection) Secondary outcome: chronic suppression after receiving antibiotics on the last day of the follow-up
Baseline Characteristics		VIP (n= 36)	Control (n= 37)	p-value
	Age, years	60.8	61.1	0.71
	Sex Male Female	24 12	23 14	0.74 - -
	Body mass index, kg/m²	31.7	31.8	0.67
	Joint being operated upon Hip Knee	20 16	18 20	0.49
	Co-Morbidities Diabetic Active smoking Immunosuppression	16 6 7	18 6 8
Results	Endpoint	VIP (n= 36)	Control (n= 37)	p-value
	Failure rate	6 (16.7 %)	14 (37 %)	< 0.05
	Type of joint failure Hips Knees	2 (10 %) 4 (25 %)	4 (22 %) 10 (50 %)	< 0.05
	Pathogens identified in failure cases MSSE^* MSSA^# Proteus mirabilis MRSA^{^} Pseudomonas aeruginosa Streptococci Enterococci	3 2 1 1 1 0 0	4 4 0 0 0 1 1
	^*Methicillin-sensitive coagulase-negative Staphylococci ^#Methicillin-sensitive Staphylococcus aureus ^{^}Methicillin-resistant Staphylococcus There were no patients on chronic antibiotic suppression at final follow-up in the control group.
Adverse Events	Common Adverse Events: no adverse events associated with VIP treatment
	Serious Adverse Events: acute renal failure was seen in one patient that was not directly related to VIP treatment
	Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions	Implementation of the VIP protocol is an economical, safe, and effective adjunct to improve the success of IDLE.
InpharmD Researcher Critique	Patients with highly virulence organisms were poorly represented in the study which may not represent the general patient population. It is unknown whether the reduced failure rate was due to povidone-iodine irrigation, vancomycin powder administration, or a combination of both.

References:

Riesgo AM, Park BK, Herrero CP, Yu S, Schwarzkopf R, Iorio R. Vancomycin Povidone-Iodine Protocol Improves Survivorship of Periprosthetic Joint Infection Treated With Irrigation and Debridement. J Arthroplasty. 2018;33(3):847-850. doi:10.1016/j.arth.2017.10.044

Pharmacokinetics of Topical and Intravenous Cefazolin in Patients with Clean Surgical Wounds
Design	Randomized, open-label prospective study N= 24
Objective	To measure cefazolin concentrations both in serum and in wound drain fluid after intravenous dosing and after irrigation
Study Groups	Intravenous (n= 12) Wound Irrigation (n= 12)
Inclusion Criteria	Patients undergoing bilateral breast reduction for macromastia
Exclusion Criteria	Age between 18 and 65 years, pregnant/nursing, sensitivity to any of the following: anticholinergics, penicillins, or cephalosporins
Methods	Patients were randomized (1:1) to receive either preoperative parenteral intravenous (IV) cefazolin (1 g per 50 mL normal saline [NS]) or intraoperative wound irrigation cefazolin (2 g per 250 mL NS). During wound closure, each wound was irrigated with either 250 mL of NS in the IV group or the cefazolin solution of 2 g per 250 mL NS and one drain was placed across each breast wound. The cefazolin concentration in both serum and wound drainage fluid was measured at various time intervals after drug administration. Therapeutic cefazolin concentrations were defined as those above the minimum therapeutic concentration to treat Staphylococcus aureus (>8 μg/mL).
Duration	Intervention: 1 time dose of cefazolin preoperatively or during wound closure Follow-up: 5 hours postoperatively, after study amendment 6 patients were followed-up 24 hours postoperatively
Outcome Measures	Serum cefazolin concentration, cefazolin concentration at the surgical site
Baseline Characteristics		Intravenous (n=12)	Wound Irrigation (n= 12)
	Median age, years	37	40
	Median body mass index, kg/m²	29	28.5
	Median weight, lbs	166.5	173
	Median height, inches	64	66
Results	Endpoint	Intravenous (n= 12)	Wound Irrigation (n= 12)	p-Value
	Median Serum Cefazolin Concentration, μg/mL Time, minutes 0 15 30 60 120 180 240 300	0.00 40.44 31.42 19.42 13.89 8.74 7.82 4.94	0.00 10.57 9.26 9.06 8.20 5.81 4.91 3.34	1.0000 0.0014 0.0039 0.0037 0.0124 0.0655 0.1020 0.0820
	Median Cefazolin Concentration at Surgical Site, μg/mL Time, minutes 15* 30* 60 120 180 240 300	22.49 21.44 20.45 18.91 16.96 10.62 9.53	4185.93 2896.02 2588.43 1886.55 1076.88 891.84 701.08	0.0006 0.0006 0.0004 0.0004 0.0004 0.0004 0.0004
	For Serum Concentration, Time 0 for Group 1 was prior to preoperative dosing, whereas Time 0 for Group 2 is at final wound closure. *one patient from Group 2 did not produce sufficient volume from wound to measure at 15 and 30 minutes.
Adverse Events	Not disclosed
Study Author Conclusions	Protective cefazolin concentrations in the wound can be achieved by both intravenous and irrigation delivery. Wound irrigation produces higher concentrations for longer periods of time.
InpharmD Researcher Critique	Due to the study amendment occurring only in the wound irrigation arm, there was no 12 or 24-hour follow-up data from the IV group to compare the results to. The study effectively assessed cefazolin levels by using a consistent draw schedule and avoiding skewed data. Results showed that topical cefazolin irrigation maintains therapeutic levels at the wound site but can drop in serum levels quickly. The minimum therapeutic concentration required to cover Staphylococcus aureus (greater than 8 μg/mL) may vary across different hospital regions.

References:

White RR 4th, Pitzer KD, Fader RC, Rajab MH, Song J. Pharmacokinetics of topical and intravenous cefazolin in patients with clean surgical wounds. Plast Reconstr Surg. 2008;122(6):1773-1779. doi:10.1097/PRS.0b013e31818d5899

Poor Outcomes of Irrigation and Debridement in Acute Periprosthetic Joint Infection With Antibiotic-impregnated Calcium Sulfate Beads
Design	Retrospective data review N= 33*
Objective	To evaluate the overall success of outcomes regarding irrigation and debridement (I&D) with implant retention for the treatment of acute periprosthetic joint infection(s) (PJI) for patients who have been applied antibiotic-impregnated calcium sulfate beads
Study Groups	All patients (n= 33*)
Inclusion Criteria	Patients undergoing irrigation and debridement with component retention and application of antibiotic-impregnated calcium sulfate beads for acute PJI
Exclusion Criteria	Not disclosed
Methods	Operative procedure consisted of a complete synovectomy, exchange of modular parts (modular line for TKA and modular femoral head/line for THA), and wound irrigation comprising the wound with diluted betadine solution for 3 minutes. Calcium sulfate beads were prepared by mixing 10mL calcium sulfate, one gram of vancomycin, and 1.2 grams of tobramycin. Paste was then applied with a spatula into bead mold and set to harden. Once cured, beads were placed into the wound prior to deep closure. All patients were given organism-specific postoperative intravenous antibiotic treatment for a minimum of six weeks and switched to a variable course of oral antibiotics.
Duration	July 2012 to March 2016
Outcome Measures	Primary: Recurrence of infection with follow-up for at least 3 months or until treatment failure
Baseline Characteristics		Treatment Group, all patients (N= 33)*
	Males	22 (67%)
	Age, years (range)	62 (32-88)
	Mean body mass index, kg/m² Mean American Society of Anesthesiologists (ASA) score Mean Charleston Comorbidity Index	31 2.7 4.8
	Acute hematogenous PJI	18 (55%)
	Acute post-op PJI	14 (42%)
	PJI Total knee arthroplasties Total knee arthroplasties	27 (82%) 6 (18%)
Results	Endpoint	Treatment Group (N= 33)*	p-value
	Failed trial overall Acute hematogenous PJI Acute post-op PJI	16 (48%) 47% 50%	0.886
	Staphylococcal, n=20 Non-staphylococcal, n=13	10 (50%) 6 (46%)	0.835
	Two-stage exchange needed for failure group, n=16	7 (44%)
	Chronic antibiotic suppression needed for failure group, n=16	9 (56%)
	Acute hem. PJI vs. acute post-op PJI BMI ASA Charleston Comorbidity Index	30.8 vs. 31.1 2.7 vs. 2.7 5.4 vs. 3.8	0.845 1.000 0.171
	*Denotes that 1 patient was categorized as bilateral Acute hematogenous PJI and was included in total sample of 33 all throughout Patients were followed for an average of 13 months (range, 3-30 months); no results listed showed the significance of the variables compared.
Adverse Events	N/A
Study Author Conclusions	The addition of antibiotic-impregnated calcium sulfate beads does not appear to improve outcomes of irrigation and debridement with implant retention in the setting of acute hematogenous or acute postoperative PJI. Given the short follow-up in this report, this represents a best-case scenario, and the overall failure rate may be higher with further follow-up.
InpharmD Researcher Critique	The study is limited by its retrospective nature, a small sample size, and a lack of a controlled group. As the study used antibiotic-impregnated calcium sulfate beads containing vancomycin, results may not readily apply to vancomycin irrigation.

References:

Flierl MA, Culp BM, Okroj KT, Springer BD, Levine BR, Della Valle CJ. Poor outcomes of irrigation and debridement in acute periprosthetic joint infection with antibiotic-impregnated calcium sulfate beads. The Journal of Arthroplasty. 2017;32(8):2505-2507. doi:10.1016/j.arth.2017.03.051