What are the alternative irrigation options for bacitracin?

Comment by InpharmD Researcher

Guidelines do not support the use of antibiotic irrigations for surgical site infection prophylaxis. However, some evidence suggest povidone-iodine, chlorhexidine, and sodium hypochlorite may be considered based available data. There is limited information on alternative antimicrobial irrigation solutions for specific surgical procedures. No data was found for port removal or podiatry. Combination antimicrobials may reduce risk of infectious complications in breast implant and CIED procedures.

  

Pubmed: antimicrobial irrigation hip knee replacement = 42 results; irrigation breast implant = 127 results; irrigation podiatry = 0 results; irrigation port removal = 61 results; irrigation Implantable Cardioverter Defibrillator = 37 results;

Background

Joint clinical practice guidelines for antimicrobial prophylaxis in surgery from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Surgical Infection Society, and the Society for Healthcare Epidemiology of America note that there is no additional benefit of topically administered antimicrobial irrigation solutions, pastes, or washes when used as adjuncts to parenteral antimicrobial prophylaxis, and that additional data are needed to support this practice. One study did show possible benefits for cefazolin 1 g/L bladder and intraabdominal irrigation as an adjunct to cefazolin IV for surgical site infection prophylaxis. [1]

A guideline update by the American College of Surgeons and Surgical Infection Society also states that there is insufficient evidence to recommend routine use of topical antimicrobial therapy to decrease the risk of surgical site infection (SSI). [2]

The Centers for Disease Control and Prevention (CDC) guideline for the prevention of SSI states that there are uncertain trade-offs between the benefits and harms of intraoperative antimicrobial irrigation and that no recommendation could be made regarding its use. These guidelines. however, say aqueous iodophor solutions can be considered for irrigation of deep or subcutaneous tissues. [3]

A 2010 review discusses the lack of literature surrounding the use of topical antibiotics during neurosurgery. Of the ten papers reviewed, only one was published after the year 2000 (range, 1947 to 1999). Some papers include agents that are not (or no longer) available in the United States. All included papers are considered low-quality evidence, with five (50%) being case series and one being an expert opinion editorial from 1982. [4]

An in vitro study evaluated the antiseptic ability of chlorhexidine, povidone-iodine, sodium hypochlorite, and triple antibacterial (bacitracin, gentamicin, and polymyxin) when used for irrigation at 1, 5, and 10 minutes. Results found chlorhexidine 0.05% and 0.1% at all three exposure times, povidone-iodine 10% at all three exposure times, and povidone-iodine 3.5% at 10 minutes only were effective at eradicating Staphylococcus epidermidis from biofilms. All concentrations and all exposure times of sodium hypochlorite and triple antibacterial solution were not effective. [6]

Total hip/knee replacement:
While not an antimicrobial agent, povidone-iodine lavage before wound closure has been investigated in a meta-analysis to determine rates of postoperative infections. Based on 7 studies, the investigation found an overall odds ratio for infection rate to be 0.67 (95% CI 0.38 to 1.19; p=0.17) for the use of povidone-iodine. Subgroup analysis did not reveal any significant differences either. While there may be a lower risk of infection with povidone-iodine, the results have demonstrated an overall lack of protection against postoperative infection. [7]

Breast implants:
A meta-analysis observing the effectiveness of breast pocket antimicrobial irrigation found significant reductions in clinical infection (risk ratio 0.52; 95% CI 0.33 to 0.81) and capsular contracture (risk ratio 0.36; 95% CI 0.16 to 0.83). Irrigation from the included studies consisted of a combination antibiotic irrigation or was unspecified. One study reported significant reduction in infection rates with cephalothin 1g + saline 1L + epinephrine 1 mg versus saline + epinephrine control. Another study reported significant reduction in capsular contracture using cefuroxime 750 mg + povidone-iodine 10 mL + gentamicin 80 mg + saline 15 mL compared to no irrigation. Other combinations may be useful but the other studies had bacitracin included in the regime or did not specify the antibiotic irrigation. [8]

A systematic review found that studies of antibiotic irrigation for implant-based breast augmentation were characterized by low-quality and high risk of bias. Only one retrospective study within the review observed an irrigation solution without bacitracin: povidone-iodine + cefuroxime + gentamicin diluted in sodium chloride. The solution had a lower rate of capsular contracture compared to standard systemic prophylaxis. The author of the systematic review believes the combination with povidone-iodine may have influenced this behavior. [9]

Cardiac/ICD implants:
The American College of Cardiology Foundation/American Heart Association Task Force and the Heart Rhythm Society's 2012 guidelines for device implant therapy of cardiac rhythm abnormalities do not provide recommendations for antibiotic irrigation. [10]

An international survey of cardiologists specializing in arrhythmia found that most utilize intraoperative antimicrobial pocket irrigation during cardiovascular implantable electronic device (CIED) infection prophylaxis. From 487 responses (response rate: 23.3%; 28.2% from the U.S.), 87% utilize antimicrobial irrigation or eluting pouch. Bacitracin was the most commonly utilize antimicrobial agent followed by vancomycin (39%), and a general cephalosporin agent (29%). The applicability of the results are limited as the survey merely gauges the provider's preferences or referencing the hospital policies. [11]

A meta-analysis for prevention of CIED pocket infection using antimicrobial pocket irrigation found significant protection (relative risk 0.42; 95% CI 0.24 to 0.75 for first-line therapy and 0.24; 95% CI 0.20 to 0.58 for second-line therapy). Antimicrobials that showed protection includes general 3rd-generation cephalosporins, ceftriaxone, cefoperazone/tazobactam, azithromycin, and combination amikacin/gentamicin. However, the studies that include povidone-iodine, clindamycin, cefazolin, and gentamicin did not observe significant protection against pocket infection. Despite overall protection being determined, the inconsistent results from individual studies leave a possibility that there is no benefit seen to irrigation. Furthermore, most studies were from China which has a different microbial landscape compared to the U.S. [12]

References:

[1] Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283.
[2] Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224(1):59-74.
[3] Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152(8):784–791.
[4] Alves RV, Godoy R. Topical antibiotics and neurosurgery: Have we forgotten to study it?. Surg Neurol Int. 2010;1:22. Published 2010 Jun 30. doi:10.4103/2152-7806.64966
[6] Schmidt K, Estes C, McLaren A, Spangehl MJ. Chlorhexidine Antiseptic Irrigation Eradicates Staphylococcus epidermidis From Biofilm: An In Vitro Study. Clin Orthop Relat Res. 2018;476(3):648–653.
[7] Kim CH, Kim H, Lee SJ, et al. The Effect of Povidone-Iodine Lavage in Preventing Infection After Total Hip and Knee Arthroplasties: Systematic Review and Meta-Analysis. J Arthroplasty. 2020;35(8):2267-2273. doi:10.1016/j.arth.2020.03.004
[8] Lynch JM, Sebai ME, Rodriguez-Unda NA, Seal S, Rosson GD, Manahan MA. Breast Pocket Irrigation with Antibiotic Solution at Implant Insertion: A Systematic Review and Meta-Analysis. Aesthetic Plast Surg. 2018;42(5):1179-1186. doi:10.1007/s00266-018-1166-2
[9] Samargandi OA, Joukhadar N, Al Youha S, Thoma A, Williams J. Antibiotic Irrigation of Pocket for Implant-Based Breast Augmentation to Prevent Capsular Contracture: A Systematic Review. Plast Surg (Oakv). 2018;26(2):110-119. doi:10.1177/2292550317747854
[10] Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2013;61(3):e6-e75. doi:10.1016/j.jacc.2012.11.007
[11] Zheng Q, Di Biase L, Ferrick KJ, et al. Use of antimicrobial agent pocket irrigation for cardiovascular implantable electronic device infection prophylaxis: Results from an international survey. Pacing Clin Electrophysiol. 2018;41(10):1298-1306. doi:10.1111/pace.13473
[12] Kang FG, Liu PJ, Liang LY, et al. Effect of pocket irrigation with antimicrobial on prevention of pacemaker pocket infection: a meta-analysis. BMC Cardiovasc Disord. 2017;17(1):256. Published 2017 Sep 30. doi:10.1186/s12872-017-0689-9

Literature Review

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

What are the alternative irrigation options for bacitracin?

Level of evidence

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



Please see Tables 1-2 for your response.


 

Efficacy of Dilute Betadine Solution Irrigation in the Prevention of Postoperative Infection of Spinal Surgery

Design

Prospective, single-blinded, randomized study

N=414 

Objective

To evaluate the efficacy of dilute betadine irrigation of spinal surgical wounds in prevention of postoperative wound infection

Study Groups

Dilute Betadine (n=208)

Normal Saline Alone (n=206)

Methods

Inclusion criteria: patients undergoing spinal surgery

Exclusion criteria: patients with overt or suspected pyogenic vertebral osteomyelitis, discitis, or any form of preoperative spinal infection; patients with fever or other suspected sources of infection

Patients were randomized to receive irrigation with betadine or normal saline during spinal surgery. Approximately 5 mL of povidone-iodine 10% was diluted with normal saline to achieve a 0.35% povidone-iodine (3.5% betadine) solution for use during operation.

All surgery was performed in standard operation theaters, without routine ultraviolet light, laminar flow, or other special air measures. Three senior surgeons who participated in our study performed all procedures. All patients received cefazolin and gentamicin after surgery for 48 hours.

Duration

Mean duration of follow-up: 15.5 months (6-24 months)

Outcome Measures

Wound infection

Baseline Characteristics

 

Total patient population (N=414)

Surgical sites

Cervical

Thoracolumbar spine

Anterior

Posterior

 

32 cases (7.7%)

382 cases (92%)

22 cases (5.3%)

392 cases (95%)

 

Dilute Betadine (n=208)

Normal Saline Alone (n=206)

P-value
Age, years  64 years 61 years 0.0682
Male to female ratio, fasting blood sugar, preoperative hemoglobin concentration, preoperative white blood cell count, operative time, operative blood loss, and volume of blood transfusion were all not significantly different between the two groups.

Results

  Dilute Betadine (n=208)

Normal Saline Alone (n=206)

P-value

Wound Infection

Superficial infection

Deep infection

0

0

7 (3.4%)

1 (0.5%) 

6 (2.9%)

0.0072

0.4976

0.0146

Infection occurred on average 14 days after the index procedure (range, 5–30 days). Wound discharge, dehiscence, and erythema at the incision site were the most common presenting features.

Of the seven cases with postoperative wound infection, all yielded positive bacteriologic cultures. Staphylococcus aureus was isolated in the wound discharge of six cases; five of them methicillin-resistant. Combined infection with Proteus mirabilis and enterococcus was noted in one case.

Adverse Events

None reported

Study Author Conclusions

In this randomized study, dilute betadine solution irrigation before wound closure significantly reduced the postoperative infection rate.

InpharmD Researcher Critique

This study had no active comparator since it was placebo-controlled. Strengths of this study include the consistency between operations and the randomized, blinded design.



References:

Cheng MT, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. Efficacy of dilute betadine solution irrigation in the prevention of postoperative infection of spinal surgery. Spine. 2005;30(15):1689-93.

 

Polymyxin and Bacitracin in the Irrigation Solution Provide No Benefit for Bacterial Killing in Vitro

Design

In vitro study

Objective

To compare the antimicrobial efficacy and cytotoxicity of an irrigation solution containing polymyxin-bacitracin with other commonly used irrigation solutions

Study Groups

Topical antibiotics (polymixin and bacitracin, vancomycin, or gentamicin)

Saline solution

Povidone-iodine

Chlorhexidine

Castile soap

Sodium hypochlorite 

Methods

Topical antibiotics (500,000-U/L polymyxin and 50,000-U/L bacitracin; 1-g/L vancomycin; or 80-mg/L gentamicin); Saline solution 0.9%; povidone-iodine 0.3%; chlorhexidine 0.05%; Castile soap 0.45%; and sodium hypochlorite 0.125% were exposed to Staphylococcus aureus and Escherichia coli colonies.

Surviving bacteria were manually counted following 1- and 3-minutes of solution exposure. 

Outcome Measures

Colony-forming units (CFU) following 1 and 3 minutes of exposure via quantitative efficacy assays

Results

 

Chlorhexidine

Povidone-iodine

Sodium hypochlorite

Polymixin-bacitracin

Gentamicin Castile soap Saline solution Vancomycin

E. coli 1 min, CFU

0 ± 0 0 ± 0 0 ± 0 37,000 ± 7,764 37,083 ± 4,332 74,750 ± 10,610 71,833 ± 7,712 66,167 ± 7,097

E. coli 3 mins, CFU

0 ± 0

0 ± 0 

0 ± 0  21,500 ± 5,317 13,833 ± 2,531 65,500 ± 8,032 63,583 ± 7,130 64,166 ± 6,262

S. aureus 1 min, CFU

0 ± 0

0 ± 0

0 ± 0  57,417 ± 4,528 47,167 ± 2,584 56,250 ± 2,988 62,000 ± 1,780 0 ± 0 
S. aureus 3 mins, CFU 0 ± 0  0 ± 0  0 ± 0  54,333 ± 6,595 27,833 ± 1,988 51,167 ± 3,386 53,833 ± 4,602 0 ± 0 

Adverse Events

Cytotoxicity in human fibroblasts, osteoblasts, and chondrocytes was seen in chlorhexidine (P=0.0001) and castile soap (P<0.0001) .

Study Author Conclusions

This study found povidone-iodine, chlorhexidine, sodium hypochlorite, and vancomycin irrigation solutions were the most efficacious against S. aureus compared with other tested solutions at both 1 and 3 minutes of exposure (P<0.0001). Polymyxin-bacitracin, Castile soap, and saline solution were the least effective and did not significantly differ from each other.

InpharmD Researcher Critique

This study provides evidence for more effective bacterial coverage with povidone-iodine, chlorhexidine, and sodium hypochlorite compared to polymixin-bacitracin and saline solution. 

Limitations include the limited extrapolability due to individual variations in human tissue compared to the in vitro samples. Irrigation solution dilution through bodily fluids, homeostasis thermoregulation, and other antimicrobial activity are not considered in an in vitro study.  



References:

Goswami K, Cho J, Foltz C, et al. Polymyxin and Bacitracin in the Irrigation Solution Provide No Benefit for Bacterial Killing in Vitro. J Bone Joint Surg Am. 2019;101(18):1689-1697.