# Bacitracin for Injection Recall: Impact on Immediate Breast Implant Surgical Outcomes

Authors: Abigail R. Tirrell; Jenna C. Bekeny; Eshetu A. Tefera; David H. Song; Kenneth L. Fan
Journal: The Breast Journal
 (2022)

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## Abstract

Background. Triple-antibiotic irrigation of breast implant pockets is a mainstay of infection prophylaxis in breast reconstruction and augmentation. The recall of bacitracin for injection due to risk of anaphylaxis and nephrotoxicity in January 2020, a staple component of the irrigation solution, has raised concern for worsened postoperative sequelae. This study aimed to investigate pre- and post-recall implant-based breast surgery to analyze the impact of bacitracin in irrigation solutions on infection rates. Methods. All implant-based breast reconstruction or augmentation surgeries from January 2019 to February 2021 were retrospectively reviewed. In a regression discontinuity study design, patients were divided into pre- and post-recall groups. Patient demographics, surgical details, and outcomes including infection rates were collected. Differences in complication rates were compared between groups and with surgical and patient factors. Results. 254 implants in 143 patients met inclusion criteria for this study, with 172 implants placed before recall and 82 placed after recall. Patients in each cohort did not differ in age, BMI, smoking status, or history of breast radiation or capsular contracture (p>0.05). All breast pockets were irrigated with antibiotic solution, most commonly bacitracin, cefazolin, gentamycin, and povidone-iodine before recall (116,67.4%) and cefazolin, gentamycin, and povidone-iodine after recall (59,72.0%). There was no difference in incidence of infection (6.4% vs. 8.5%, p=0.551) or cellulitis (3.5% vs. 3.7%, p=0.959) before and after recall. Implant infection was associated with smoking history (p<0.001) and increased surgical time (p=0.003). Conclusions. Despite the recent recall of bacitracin from inclusion in breast pocket irrigation solutions, our study demonstrated no detrimental impact on immediate complication rates. This shift in irrigation protocols calls for additional investigations into optimizing antibiotic combinations in solution, as bacitracin is no longer a viable option, to improve surgical outcomes and long-term benefits.


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## Body

## 1. Introduction

Irrigation of breast implant pockets is a cornerstone for preventing infectious sequelae during implant-based breast reconstruction and augmentation. Postoperative infections of breast implant cases range between 1% and 35% [1]. Infections require antibiotic therapy, lead to undesired reoperations, and yield unsatisfactory results. For patients undergoing breast reconstruction after oncologic resection, postoperative infection is associated with delays in oncologic treatment [2]. Biofilm formation from inflammation and infections within the prosthetic pocket and capsule can contribute to subsequent capsular contracture (CC), a painful and distorting complication of breast implant surgery [1, 3].Research has repeatedly demonstrated the benefits of antibiotic irrigation of breast pockets in reducing both bacterial load and rates of postoperative infection [4, 5]. Adams et al. explored the clinical efficacy of antibiotic irrigations, and their recommendation of a triple-antibiotic solution comprised of a cephalosporin, bacitracin, and gentamycin became the gold standard for intraoperative infection prevention in breast implant cases [4]. Even so, a consensus on optimal antibiotics to include has not been reached, and a variety of combinations is used among plastic surgeons in the United States [6]. The off-label use of povidone-iodine, an antiseptic, in irrigation has also been inconsistent [6]. Prior to 2000, povidone-iodine was commonly implemented as an irrigation material for breast implants; however, a moratorium on its use in irrigation was enacted by the US Food and Drug Administration (FDA) over concerns about silicone implant degradation [7]. Since its return to the market in 2017, it has been reintroduced to irrigation solutions by many plastic surgeons [6, 7].On January 31, 2020, the FDA requested the withdrawal of bacitracin for injection after the Antimicrobial Drugs Advisory Committee deemed that its benefits were outweighed by its risks of nephrotoxicity and anaphylaxis [8, 9]. Though it has been used regularly for intraoperative irrigation in many surgical fields to prevent infection, it is now only approved for use in infant pneumonia and empyema [10]. Since bacitracin previously served as a staple antibiotic in breast implant irrigation solutions, concerns for worse postoperative outcomes have risen as a result of this recall.Despite the potential for unfavorable results after the removal of bacitracin from irrigation solutions, this recall has provided an opportunity to reassess antimicrobial breast implant irrigation through a regression discontinuity experiment [11]. Therefore, the central aim of this study was to investigate outcomes after implant-based breast surgery before and after recall and analyze the impact bacitracin truly had on outcomes in the immediate postoperative period.


## 2. Methods

### 2.1. Study Design

All breast reconstruction or augmentation surgeries that involved the placement or exchange of silicone breast implants from January 2019 to February 2021 were retrospectively reviewed. Through a regression discontinuity study design, patients were divided into two groups based on the date of bacitracin for injection recall (January 31, 2020). Patients were excluded from analysis if their surgery involved placement of tissue expanders or revisional surgeries without implant exchange. A minimum period of six months of postoperative follow-up was required for inclusion in this analysis to allow for adequate time after the index surgery. This study was approved by the Institution Review Board (MHRI 2018-173).


### 2.2. Antimicrobial Surgical Technique

Surgical sites were prepared with 2% chlorhexidine gluconate in 70% isopropyl alcohol. All patients received standard systemic prophylaxis consisting of 2 grams of IV cefazolin unless an existing allergy required the use of an alternative antibiotic. Intraoperatively, all patients underwent antibiotic irrigation of the breast pocket(s). Gloves were changed prior to handling the breast implant, and an aseptic technique of implant placement was performed using a sterile surgical funnel. Implant manipulation after insertion into the breast pocket was minimized.


### 2.3. Data Collection

Demographic and comorbidity information including age, race, body mass index (BMI), and smoking history was collected. Charlson comorbidity index (CCI) scores were calculated to determine comorbidity burdens. Preoperative risk factors including a history of breast radiation, capsular contracture, or prior non-autologous reconstruction with an implant or tissue expander (TE) were recorded.Details of surgical procedures were collected, including type of surgery. In patients who underwent reconstruction after oncologic resection, type of primary surgery, such as mastectomy or lumpectomy, was recorded. Reconstructive surgeries were also defined as immediate reconstruction with an implant, delayed-immediate reconstruction in which a TE was placed initially with subsequent exchange to an implant, and delayed reconstruction. Other details collected included surgical time, implant volume, use of acellular dermal matrix (ADM), and implant surgical plane. Type of irrigation solution was noted. The type and number of antibiotic and antiseptic additives were recorded. Surgical complications were collected, including infection, cellulitis, seroma, hematoma, and delayed healing. A follow-up period for each patient was determined.


### 2.4. Statistical Analysis

Continuous variables were described by means and standard deviations, and categorical variables were described by frequencies and percentages. Two-samplet-test was used to examine differences in the averages of continuous variables between groups when normality assumption was satisfied. Chi-squared test and Fisher’s exact test compared differences in categorial frequencies between groups as appropriate. Bivariate analysis was performed to assess associations between complication rates and patient or surgical characteristics. Statistical analysis was performed using STATA v.15 (StataCorp, College Station, Texas) with significance defined as p≤0.05.


## 2.1. Study Design

All breast reconstruction or augmentation surgeries that involved the placement or exchange of silicone breast implants from January 2019 to February 2021 were retrospectively reviewed. Through a regression discontinuity study design, patients were divided into two groups based on the date of bacitracin for injection recall (January 31, 2020). Patients were excluded from analysis if their surgery involved placement of tissue expanders or revisional surgeries without implant exchange. A minimum period of six months of postoperative follow-up was required for inclusion in this analysis to allow for adequate time after the index surgery. This study was approved by the Institution Review Board (MHRI 2018-173).


## 2.2. Antimicrobial Surgical Technique

Surgical sites were prepared with 2% chlorhexidine gluconate in 70% isopropyl alcohol. All patients received standard systemic prophylaxis consisting of 2 grams of IV cefazolin unless an existing allergy required the use of an alternative antibiotic. Intraoperatively, all patients underwent antibiotic irrigation of the breast pocket(s). Gloves were changed prior to handling the breast implant, and an aseptic technique of implant placement was performed using a sterile surgical funnel. Implant manipulation after insertion into the breast pocket was minimized.


## 2.3. Data Collection

Demographic and comorbidity information including age, race, body mass index (BMI), and smoking history was collected. Charlson comorbidity index (CCI) scores were calculated to determine comorbidity burdens. Preoperative risk factors including a history of breast radiation, capsular contracture, or prior non-autologous reconstruction with an implant or tissue expander (TE) were recorded.Details of surgical procedures were collected, including type of surgery. In patients who underwent reconstruction after oncologic resection, type of primary surgery, such as mastectomy or lumpectomy, was recorded. Reconstructive surgeries were also defined as immediate reconstruction with an implant, delayed-immediate reconstruction in which a TE was placed initially with subsequent exchange to an implant, and delayed reconstruction. Other details collected included surgical time, implant volume, use of acellular dermal matrix (ADM), and implant surgical plane. Type of irrigation solution was noted. The type and number of antibiotic and antiseptic additives were recorded. Surgical complications were collected, including infection, cellulitis, seroma, hematoma, and delayed healing. A follow-up period for each patient was determined.


## 2.4. Statistical Analysis

Continuous variables were described by means and standard deviations, and categorical variables were described by frequencies and percentages. Two-samplet-test was used to examine differences in the averages of continuous variables between groups when normality assumption was satisfied. Chi-squared test and Fisher’s exact test compared differences in categorial frequencies between groups as appropriate. Bivariate analysis was performed to assess associations between complication rates and patient or surgical characteristics. Statistical analysis was performed using STATA v.15 (StataCorp, College Station, Texas) with significance defined as p≤0.05.


## 3. Results

143 patients underwent breast augmentation or reconstruction surgery with 254 implants between January 2019 and February 2021. 172 implants were placed before recall in 97 patients, and 82 implants were placed after recall in 46 patients.


### 3.1. Patient Demographics, Comorbidities, and Breast History

Patient demographic and comorbidity characteristics are described in Table1. The average patient age was 50.9 years (SD: 11.9) in the pre-recall group and 53.8 years (SD: 12.7) in the post-recall group (p=0.079). There was no difference between the two groups in CCI or patient-reported race (p>0.05). Average patient BMI was 26.1 kg/m2 (SD: 5.1) and 26.3 kg/m2 (SD: 4.6) in the pre- and post-recall groups, respectively (p=0.662). Over 70% of patients had no history of smoking in both groups, with no statistically significant difference between groups (p=0.332).Table 1
Patient demographics and comorbidities.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueAge, years51.83 ± 12.2050.90 ± 11.8653.78 ± 12.730.079BMI, kg/m226.14 ± 4.9426.05 ± 5.1026.34 ± 4.610.662CCI1.48 ± 1.001.49 ± 1.051.45 ± 0.900.783Smoking historyNever smoker187 (73.62)124 (72.09)63 (76.83)0.332Former smoker63 (24.80)44 (25.58)19 (23.17)Current smoker4 (1.57)4 (2.33)0 (0.00)Race/ethnicityWhite152 (59.84)100 (58.14)52 (63.41)0.143African American67 (26.38)52 (30.23)15 (18.29)Asian16 (6.30)10 (5.81)6 (7.32)Other19 (7.48)10 (5.81)9 (10.98)BMI: body mass index, CCI: Charlson comorbidity index. Bold values indicate statistical significance.Both groups had similar rates of implants in place prior to surgery (50.6% versus 54.9%;p=0.029); however, more patients had tissue expanders in place before recall in comparison with after recall (31.4% versus 17.1%; p=0.029) (Table 2). 16.1% of breasts operated on had a history of radiation therapy, with 29 (16.9%) in the pre-recall group and 12 (14.6%) in the post-recall group (p=0.652). A history of capsular contracture was present in 12.6% of breasts, with no difference between groups (p=0.080).Table 2
Breast history.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueHistory of breast radiation therapy41 (16.14)29 (16.86)12 (14.63)0.652History of capsular contracture32 (12.60)26 (15.12)6 (7.32)0.080Prior prosthetic deviceImplant132 (51.97)87 (50.58)45 (54.88)0.029Tissue expander68 (26.77)54 (31.40)14 (17.07)None54 (21.26)31 (18.02)23 (23.05)Bold values indicate statistical significance.


### 3.2. Surgical Details

Most surgeries were cancer reconstruction procedures, with 162 (94.2%) pre-recall procedures and 75 (91.5%) post-recall procedures involving implant-based oncologic reconstruction (p=0.417) (Table 3). Table 4 specifies the details of oncologic surgery history and reconstruction timing in those patients. Pre-recall patients had more nipple-sparing mastectomies (NSM) (65.4% versus 50.7%) and less skin-sparing mastectomies (SSM) (34.7% versus 27.8%) when compared with post-recall ones (p=0.018). Other surgeries performed included simple mastectomies and modified radical mastectomies; only one lumpectomy was performed in each group. The two groups differed in reconstruction timing, with fewer immediate reconstructions (17.3% versus 30.7%) and more delayed-immediate reconstructions (29.6% versus 20.0%) in the pre-recall group (p=0.045).Table 3
Surgical details.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueSurgery typeAugmentation17 (6.69)10 (5.81)7 (8.54)0.417Cancer reconstruction237 (93.31)162 (94.19)75 (91.46)Surgical time130.11 ± 66.19122.71 ± 66.57145.84 ± 62.950.009Implant volume448.19 ± 143.16452.41 ± 140.80439.32 ± 148.480.497Use of acellular dermal matrix141 (55.51)89 (51.74)52 (63.41)0.080Implant surgical planePre-pectoral231 (90.94)157 (91.28)74 (90.24)0.788Retro-pectoral23 (9.06)15 (8.72)8 (9.76)Irrigation solution0.9% Normal saline252 (99.21)170 (98.84)82 (100.00)0.327Lactated Ringer’s2 (0.79)2 (1.16)0 (0.00)Number of antibiotic additives111 (4.33)5 (2.91)6 (7.32)<0.001292 (36.22)24 (13.95)68 (82.93)3151 (59.45)143 (83.14)8 (9.76)Antibiotics usedBacitracin172 (67.72)172 (100.00)0 (0.00)<0.001Cefazolin212 (83.46)142 (82.56)70 (85.37)0.573Gentamycin245 (96.46)165 (95.93)80 (97)0.511Vancomycin8 (3.15)2 (1.16)6 (7.32)0.009Polymyxin B10 (3.94)0 (0.00)10 (12.20)<0.001Povidone-iodine 10%216 (85.04)144 (83.72)72 (87.80)0.394Bold values indicate statistical significance.Table 4
Oncologic reconstruction details.
Total (n = 237)Pre-recall (n = 162)Post-recall (n = 75)p valueBreast cancer surgeryNipple-sparing mastectomy144 (60.76)106 (65.43)38 (50.67)0.018Skin-sparing mastectomy71 (29.96)45 (27.78)26 (34.67)Simple mastectomy8 (3.38)2 (1.23)6 (8.00)Modified radical mastectomy8 (3.38)6 (3.70)2 (2.67)Radical mastectomy2 (0.84)0 (0.00)2 (2.67)Total mastectomy2 (0.84)2 (1.23)0 (0.00)Lumpectomy2 (0.84)1 (0.62)1 (1.33)Reconstruction timingImmediate51 (21.52)28 (17.28)23 (30.67)0.045Delayed-immediate63 (26.58)48 (29.63)15 (20.00)Delayed123 (51.90)86 (53.09)37 (49.33)Bold values indicate statistical significance.In both groups, all incisions were either inframammary (IM) or transverse incisions. Additional surgical details are displayed in Table3. All implants were silicone, and average implant volume did not differ before and after recall (452.4 mL versus 439.3 mL; p=0.497). There was no difference in implant plane between groups, with over 90% of implants placed in the pre-pectoral position (p=0.788). Use of ADM during reconstruction was more prevalent after recall, with 63.41% of implants placed with ADM after recall and 51.74% of implants before recall, though this difference was not statistically significant (p=0.08). Average surgical time was 122.7 minutes (SD: 66.6) before recall and 145.8 minutes (SD: 63.0) after recall (p=0.009).


### 3.3. Antimicrobial Irrigation Components

The most irrigation solution used was 0.9% normal saline (NS), with only two implants (1.2%) in the pre-recall group irrigated in lactated Ringer’s solution (p=0.327) (Table 3). Before recall, most irrigation solutions were composed of triple-antibiotic solution (83.1%), while most post-recall solutions were double-antibiotic ones (82.9%) (p<0.001). Antibiotics used before recall included bacitracin 50,000 units, cefazolin 1 gram, gentamycin sulfate 80 milligrams, vancomycin 1 gram, and polymyxin B 500,000 units in varying combinations according to patient allergies; the same antibiotics, except for bacitracin, were used after recall. Povidone-iodine 10% solution was used in solutions in 83.7% of pre-recall and 87.8% of post-recall surgeries.Table5 describes the antibiotic and antiseptic combinations added to irrigation before and after recall. The most common pre-recall composition was a triple-antibiotic solution of bacitracin, cefazolin, and gentamycin with povidone-iodine in 67.4% of implants; the same triple-antibiotic solution without povidone-iodine was used in 14.0% of implants. After recall, 72.0% of implants were irrigated with a double-antibiotic solution of cefazolin and gentamycin with povidone-iodine.Table 5
Antibiotic and antiseptic irrigation components.
Irrigation componentsImplants irrigatedPre-recall (n = 172)Bacitracin, cefazolin, gentamycin + povidone-iodine116 (67.44)Bacitracin, cefazolin, gentamycin24 (13.95)Bacitracin, gentamycin + povidone-iodine22 (12.79)Bacitracin4 (2.33)Bacitracin, gentamycin, vancomycin + povidone-iodine2 (1.16)Bacitracin, cefazolin + povidone-iodine2 (1.16)Bacitracin + povidone-iodine2 (1.16)Post-Recall (n = 82)Cefazolin, gentamycin + povidone-iodine59 (71.95)Cefazolin, gentamycin, polymyxin B + povidone-iodine5 (6.10)Gentamycin, vancomycin + povidone-iodine4 (4.88)Cefazolin, gentamycin3 (3.66)Gentamycin, vancomycin, polymyxin B2 (2.44)Gentamycin, polymyxin B + povidone-iodine2 (2.44)Gentamycin + povidone-iodine2 (2.44)Cefazolin2 (2.44)Gentamycin2 (2.44)Cefazolin, gentamycin, polymyxin B1 (1.22)Bold values indicate statistical significance.


### 3.4. Surgical Complications

Complications are displayed in Table6. The overall complication rate was 9.84%, with no difference between groups (9.88% versus 9.76%; p=0.952). Average implant infection and cellulitis rates were 7.1% and 3.5%, respectively, with no significant difference before and after recall (p>0.05). Other complications included seroma in 2.0% of patients, hematoma in 1.2% of patients, and delayed healing in 0.8% of patients, with no differences between groups (p=0.329). Average follow-up period was 357.1 days (SD: 307.6) before recall and 168.5 days (SD: 119.0) after recall (p<0.001).Table 6
Pre- and post-recall outcomes.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueComplicationsAny complication25 (9.84)17 (9.88)8 (9.76)0.952Infection18 (7.09)11 (6.40)7 (8.54)0.551Cellulitis9 (3.54)6 (3.49)3 (3.66)0.959Other complications10 (3.94)6 (3.49)4 (4.88)0.329Seroma5 (1.97)2 (1.16)3 (3.66)Hematoma3 (1.18)2 (1.16)1 (1.22)Delayed healing2 (0.79)2 (1.16)0 (0.00)Follow-up period, days296.22 ± 276.23357.10 ± 307.64168.51 ± 118.96<0.001Bold values indicate statistical significance.Table7 reveals complication rates specific to cases that utilized the gold standard triple-antibiotic irrigation solution before recall (bacitracin, cefazolin, gentamycin + povidone-iodine) and double-antibiotic solution after recall (cefazolin, gentamycin + povidone-iodine). There was no difference between pre- and post-recall cohorts in overall complication rate (16.38% versus 10.17%; p=0267) or infection rates (5.17% versus 8.47%; p=0.395). There was a significant decrease in other complications, including seroma, hematoma, and delayed healing (11.21% versus 1.69%; p=0.028) after the recall.Table 7
Complication rates with gold standard antibiotic combinations∗.
Total (n = 175)Pre-recall (n = 116)Post-recall (n = 59)p valueComplicationsAny complication25 (14.29)19 (16.38)6 (10.17)0.267Infection11 (6.29)6 (5.17)5 (8.47)0.395Cellulitis5 (2.86)4 (3.45)1 (1.69)0.510Other Complications14 (8.00)13 (11.21)1 (1.69)0.028∗Gold standard antibiotic combinations indicate the use of bacitracin + cefazolin + gentamycin with povidone-iodine before recall, and cefazolin + gentamycin with povidone-iodine after recall. Bold values indicate statistical significance.Patient and surgical factors were analyzed for association with complications in Table8. Patient history of smoking, breast radiation, and increased surgical time was associated with the development of “any complication” (p<0.05). Implant infection was associated with patient history of smoking, no history of prior prosthetic device, and increased surgical time (p>0.05). Cellulitis was associated with longer surgical time (0.044). Table 9 sub-stratified patient populations into smaller, more homogenous groups based on surgery type, history of radiation, use of ADM, prior prosthetic device, and reconstructive timing. With the exception of fewer overall complications in the cohort of patients with prior implant or TE after the recall (16.31% versus 3.39%; p=0.012), there was no change in complication rates after the recall in any patient subpopulation (p<0.001).Table 8
Outcomes by patient and surgical factors.
ComplicationYesNop valueAny complication (n = 25)Age54.64 ± 13.3551.56 ± 12.100.234BMI27.96 ± 5.9225.99 ± 4.780.059CCI1.60 ± 0.871.48 ± 1.010.555Smoking historyNever smoker16 (64.00)169 (74.45)<0.001Former smoker6 (24.00)57 (25.11)Current smoker3 (12.00)1 (0.44)History of breast radiation therapy8 (32.00)33 (14.54)0.025History of capsular contracture5 (20.00)25 (11.01)0.188Prior prosthetic deviceTissue expander6 (24.00)62 (27.31)0.053Implant9 (36.00)121 (53.30)None10 (40.00)44 (19.38)Surgery typeAugmentation0 (0.00)17 (7.49)0.157Reconstruction25 (100.00)210 (92.51)Total surgical time186.96 ± 97.68124.25 ± 58.96<0.001Implant volume498.20 ± 140.76441.78 ± 142.940.062Implant surgical planePre-Pectoral24 (96.00)205 (90.31)0.348Retro-pectoral1 (4.00)22 (9.69)Use of acellular dermal matrix17 (68.00)124 (54.63)0.201Number of antibiotics2.44 ± 0.652.57 ± 0.570.294Povidone-iodine 10%20 (80.00)194 (95.46)0.469Infection (n = 18)Age54.58 ± 14.9351.62 ± 11.980.322BMI28.48 ± 6.0425.96 ± 4.810.037CCI1.56 ± 0.861.47 ± 1.010.728Smoking historyNever smoker10 (55.56)177 (75.00)<0.001Former smoker5 (27.78)58 (24.58)Current smoker3 (16.67)1 (0.42)History of breast radiation therapy5 (27.78)36 (15.25)0.164History of capsular contracture2 (1.11)30 (12.71)0.844Prior prosthetic deviceTissue expander4 (22.22)64 (27.12)0.007Implant5 (27.78)127 (53.81)None9 (50.00)45 (19.07)Surgery typeAugmentation0 (0.00)17 (7.20)0.238Reconstruction18 (100.00)219 (92.80)Total surgical time174.72 ± 87.97126.70 ± 63.180.003Implant volume510.56 ± 120.26443.43 ± 143.870.055Implant surgical planePre-pectoral17 (94.44)214 (90.68)0.591Retro-pectoral1 (5.56)22 (9.32)Use of acellular dermal matrix12 (66.67)129 (54.66)0.323Number of antibiotics2.33 ± 0.692.57 ± 0.570.098Povidone-iodine 10%14 (37.84)202 (93.09)0.370Cellulitis (n = 9)Age52.94 ± 13.3551.79 ± 12.180.781BMI23.85 ± 2.6426.22 ± 4.990.157CCI1.33 ± 1.001.48 ± 1.000.663Smoking historyNever smoker6 (66.67)181 (73.88)0.786Former smoker3 (33.33)60 (24.49)Current smoker0 (0.00)4 (1.63)History of breast radiation therapy3 (33.33)38 (15.51)0.153History of capsular contracture2 (22.22)30 (12.24)0.376Prior prosthetic deviceTissue expander1 (1.11)67 (27.35)0.191Implant4 (4.44)128 (52.24)None4 (4.44)50 (20.41)Surgery typeAugmentation0 (0.00)17 (6.94)0.413Reconstruction9 (100.00)228 (93.06)Total surgical time173.67 ± 85.31128.51 ± 65.050.044Implant volume477.78 ± 155.85447.10 ± 142.910.529Implant surgical planePre-pectoral9 (100.00)222 (90.61)0.335Retro-pectoral0 (0.00)23 (9.39)Use of acellular dermal matrix5 (55.56)136 (55.51)0.998Number of antibiotics2.56 ± 0.532.55 ± 0.580.982Povidone-iodine 10%8 (88.89)208 (84.90)0.742BMI: body mass index, CCI: Charlson comorbidity index. Bold values indicate statistical significance.Table 9
Sub-stratification of case outcomes.
TotalPre-recallPost-recallp valueSurgery typeReconstructiven = 237n = 162n = 75Number of antibiotics2.53 ± 0.592.79 ± 0.481.97 ± 0.37<0.001ComplicationsAny complication37 (15.62)28 (17.28)9 (12.00)0.297Infection18 (7.59)11 (6.79)7 (9.33)0.492Cellulitis9 (3.80)6 (3.70)3 (4.00)0.912Other complications10 (4.22)6 (3.70)4 (5.33)0.562Augmentationn = 17n = 10n = 7Number of antibiotics2.82 ± 0.393.00 ± 02.57 ± 0.530.103ComplicationsAny complication0 (0.00)0 (0.00)0 (0.00)1.0Infection0 (0.00)0 (0.00)0 (0.00)1.0Cellulitis0 (0.00)0 (0.00)0 (0.00)1.0Other complications0 (0.00)0 (0.00)0 (0.00)1.0History of breast radiationPrior RTn = 34n = 26n = 8Number of antibiotics2.65 ± 0.492.84 ± 0.382.00 ± 0.00<0.001ComplicationsAny complication12 (35.29)11 (42.31)1 (12.50)0.123Infection4 (11.76)3 (11.54)1 (12.50)0.941Cellulitis2 (5.88)2 (7.69)0 (0.00)0.419Other complications3 (8.82)3 (11.54)0 (0.00)0.314No prior RTn = 208n = 134n = 74Number of antibiotics2.51 ± 0.602.78 ± 0.502.03 ± 0.44<0.001ComplicationsAny complication25 (12.02)17 (12.69)8 (10.81)0.690Infection14 (6.73)8 (5.97)6 (8.11)0.556Cellulitis7 (3.37)4 (2.99)3 (4.05)0.682Other complications7 (3.37)3 (2.24)4 (5.41)0.225Use of acellular dermal matrixADM usedn = 86n = 49n = 37Number of antibiotics2.48 ± 0.552.80 ± 0.412.05 ± 040<0.001ComplicationsAny complication15 (17.44)7 (14.29)8 (21.62)0.375Infection9 (10.47)3 (6.12)6 (16.22)0.130Cellulitis5 (5.81)2 (4.08)3 (8.11)0.430Other complications6 (6.98)2 (4.08)4 (10.81)0.225ADM not usedn = 168n = 123n = 45Number of antibiotics2.59 ± 0.592.80 ± 0.492.00 ± 0.43<0.001ComplicationsAny complication22 (13.10)21 (17.07)1 ()0.012Infection9 (5.36)8 (6.50)1 ()0.275Cellulitis4 (2.38)4 (3.25)0 (0.00)0.221Other complications4 (2.38)4 (3.25)0 (0.00)0.221Reconstruction timingImmediaten = 51n = 28n = 23Number of antibiotics2.57 ± 0.502.89 ± 0.312.17 ± 0.39<0.001ComplicationsAny complication13 (25.50)6 (21.43)7 (30.43)0.463Infection10 (19.61)4 (14.29)6 (26.09)0.291Cellulitis5 (9.80)2 (7.14)3 (13.0)0.481Other complications4 (7.84)1 (3.57)3 ()0.211Delayed-immediaten = 63n = 48n = 15Number of antibiotics2.56 ± 0.622.77 ± 0.521.87 ± 0.35<0.001ComplicationsAny complication9 ()9 ()0 ()0.070Infection3 ()3 ()0 ()0.321Cellulitis0 ()0 ()0 ()1.0Other complications2 ()2 ()0 ()0.422Delayedn = 123n = 86n = 37Number of antibiotics2.50 ± 0.612.77 ± 0.501.89 ± 0.31<0.001ComplicationsAny complication15 ()13 ()2 ()0.131Infection5 ()4 ()1 ()0.616Cellulitis4 ()4 ()0 ()0.182Other complications4 ()3 ()1 ()0.822History of prosthetic devicePrior implant or TEn = 200n = 141n = 59Number of antibiotics2.54 ± 0.602.78 ± 0.491.97 ± 0.41<0.001ComplicationsAny complication25 (12.50)23 (16.31)2 (3.39)0.012Infection9 (4.50)8 (5.67)1 (1.69)0.216Cellulitis5 (2.50)5 (3.55)0 (0.00)0.143Other complications6 (3.00)5 (3.55)1 (1.69)0.484No prior devicen = 54n = 31n = 23Number of antibiotics2.59 ± 0.502.90 ± 0.302.17 ± 0.39<0.001ComplicationsAny complication12 (2.22)5 (16.13)7 (30.43)0.211Infection9 (16.67)3 (9.68)6 (26.09)0.110Cellulitis4 (7.41)1 (3.23)3 (13.04)0.173Other complications4 (7.41)1 (3.23)3 (13.04)0.173RT: radiation therapy, ADM: acellular dermal matrix, TE: tissue expander. Bold values indicate statistical significance.


## 3.1. Patient Demographics, Comorbidities, and Breast History

Patient demographic and comorbidity characteristics are described in Table1. The average patient age was 50.9 years (SD: 11.9) in the pre-recall group and 53.8 years (SD: 12.7) in the post-recall group (p=0.079). There was no difference between the two groups in CCI or patient-reported race (p>0.05). Average patient BMI was 26.1 kg/m2 (SD: 5.1) and 26.3 kg/m2 (SD: 4.6) in the pre- and post-recall groups, respectively (p=0.662). Over 70% of patients had no history of smoking in both groups, with no statistically significant difference between groups (p=0.332).Table 1
Patient demographics and comorbidities.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueAge, years51.83 ± 12.2050.90 ± 11.8653.78 ± 12.730.079BMI, kg/m226.14 ± 4.9426.05 ± 5.1026.34 ± 4.610.662CCI1.48 ± 1.001.49 ± 1.051.45 ± 0.900.783Smoking historyNever smoker187 (73.62)124 (72.09)63 (76.83)0.332Former smoker63 (24.80)44 (25.58)19 (23.17)Current smoker4 (1.57)4 (2.33)0 (0.00)Race/ethnicityWhite152 (59.84)100 (58.14)52 (63.41)0.143African American67 (26.38)52 (30.23)15 (18.29)Asian16 (6.30)10 (5.81)6 (7.32)Other19 (7.48)10 (5.81)9 (10.98)BMI: body mass index, CCI: Charlson comorbidity index. Bold values indicate statistical significance.Both groups had similar rates of implants in place prior to surgery (50.6% versus 54.9%;p=0.029); however, more patients had tissue expanders in place before recall in comparison with after recall (31.4% versus 17.1%; p=0.029) (Table 2). 16.1% of breasts operated on had a history of radiation therapy, with 29 (16.9%) in the pre-recall group and 12 (14.6%) in the post-recall group (p=0.652). A history of capsular contracture was present in 12.6% of breasts, with no difference between groups (p=0.080).Table 2
Breast history.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueHistory of breast radiation therapy41 (16.14)29 (16.86)12 (14.63)0.652History of capsular contracture32 (12.60)26 (15.12)6 (7.32)0.080Prior prosthetic deviceImplant132 (51.97)87 (50.58)45 (54.88)0.029Tissue expander68 (26.77)54 (31.40)14 (17.07)None54 (21.26)31 (18.02)23 (23.05)Bold values indicate statistical significance.


## 3.2. Surgical Details

Most surgeries were cancer reconstruction procedures, with 162 (94.2%) pre-recall procedures and 75 (91.5%) post-recall procedures involving implant-based oncologic reconstruction (p=0.417) (Table 3). Table 4 specifies the details of oncologic surgery history and reconstruction timing in those patients. Pre-recall patients had more nipple-sparing mastectomies (NSM) (65.4% versus 50.7%) and less skin-sparing mastectomies (SSM) (34.7% versus 27.8%) when compared with post-recall ones (p=0.018). Other surgeries performed included simple mastectomies and modified radical mastectomies; only one lumpectomy was performed in each group. The two groups differed in reconstruction timing, with fewer immediate reconstructions (17.3% versus 30.7%) and more delayed-immediate reconstructions (29.6% versus 20.0%) in the pre-recall group (p=0.045).Table 3
Surgical details.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueSurgery typeAugmentation17 (6.69)10 (5.81)7 (8.54)0.417Cancer reconstruction237 (93.31)162 (94.19)75 (91.46)Surgical time130.11 ± 66.19122.71 ± 66.57145.84 ± 62.950.009Implant volume448.19 ± 143.16452.41 ± 140.80439.32 ± 148.480.497Use of acellular dermal matrix141 (55.51)89 (51.74)52 (63.41)0.080Implant surgical planePre-pectoral231 (90.94)157 (91.28)74 (90.24)0.788Retro-pectoral23 (9.06)15 (8.72)8 (9.76)Irrigation solution0.9% Normal saline252 (99.21)170 (98.84)82 (100.00)0.327Lactated Ringer’s2 (0.79)2 (1.16)0 (0.00)Number of antibiotic additives111 (4.33)5 (2.91)6 (7.32)<0.001292 (36.22)24 (13.95)68 (82.93)3151 (59.45)143 (83.14)8 (9.76)Antibiotics usedBacitracin172 (67.72)172 (100.00)0 (0.00)<0.001Cefazolin212 (83.46)142 (82.56)70 (85.37)0.573Gentamycin245 (96.46)165 (95.93)80 (97)0.511Vancomycin8 (3.15)2 (1.16)6 (7.32)0.009Polymyxin B10 (3.94)0 (0.00)10 (12.20)<0.001Povidone-iodine 10%216 (85.04)144 (83.72)72 (87.80)0.394Bold values indicate statistical significance.Table 4
Oncologic reconstruction details.
Total (n = 237)Pre-recall (n = 162)Post-recall (n = 75)p valueBreast cancer surgeryNipple-sparing mastectomy144 (60.76)106 (65.43)38 (50.67)0.018Skin-sparing mastectomy71 (29.96)45 (27.78)26 (34.67)Simple mastectomy8 (3.38)2 (1.23)6 (8.00)Modified radical mastectomy8 (3.38)6 (3.70)2 (2.67)Radical mastectomy2 (0.84)0 (0.00)2 (2.67)Total mastectomy2 (0.84)2 (1.23)0 (0.00)Lumpectomy2 (0.84)1 (0.62)1 (1.33)Reconstruction timingImmediate51 (21.52)28 (17.28)23 (30.67)0.045Delayed-immediate63 (26.58)48 (29.63)15 (20.00)Delayed123 (51.90)86 (53.09)37 (49.33)Bold values indicate statistical significance.In both groups, all incisions were either inframammary (IM) or transverse incisions. Additional surgical details are displayed in Table3. All implants were silicone, and average implant volume did not differ before and after recall (452.4 mL versus 439.3 mL; p=0.497). There was no difference in implant plane between groups, with over 90% of implants placed in the pre-pectoral position (p=0.788). Use of ADM during reconstruction was more prevalent after recall, with 63.41% of implants placed with ADM after recall and 51.74% of implants before recall, though this difference was not statistically significant (p=0.08). Average surgical time was 122.7 minutes (SD: 66.6) before recall and 145.8 minutes (SD: 63.0) after recall (p=0.009).


## 3.3. Antimicrobial Irrigation Components

The most irrigation solution used was 0.9% normal saline (NS), with only two implants (1.2%) in the pre-recall group irrigated in lactated Ringer’s solution (p=0.327) (Table 3). Before recall, most irrigation solutions were composed of triple-antibiotic solution (83.1%), while most post-recall solutions were double-antibiotic ones (82.9%) (p<0.001). Antibiotics used before recall included bacitracin 50,000 units, cefazolin 1 gram, gentamycin sulfate 80 milligrams, vancomycin 1 gram, and polymyxin B 500,000 units in varying combinations according to patient allergies; the same antibiotics, except for bacitracin, were used after recall. Povidone-iodine 10% solution was used in solutions in 83.7% of pre-recall and 87.8% of post-recall surgeries.Table5 describes the antibiotic and antiseptic combinations added to irrigation before and after recall. The most common pre-recall composition was a triple-antibiotic solution of bacitracin, cefazolin, and gentamycin with povidone-iodine in 67.4% of implants; the same triple-antibiotic solution without povidone-iodine was used in 14.0% of implants. After recall, 72.0% of implants were irrigated with a double-antibiotic solution of cefazolin and gentamycin with povidone-iodine.Table 5
Antibiotic and antiseptic irrigation components.
Irrigation componentsImplants irrigatedPre-recall (n = 172)Bacitracin, cefazolin, gentamycin + povidone-iodine116 (67.44)Bacitracin, cefazolin, gentamycin24 (13.95)Bacitracin, gentamycin + povidone-iodine22 (12.79)Bacitracin4 (2.33)Bacitracin, gentamycin, vancomycin + povidone-iodine2 (1.16)Bacitracin, cefazolin + povidone-iodine2 (1.16)Bacitracin + povidone-iodine2 (1.16)Post-Recall (n = 82)Cefazolin, gentamycin + povidone-iodine59 (71.95)Cefazolin, gentamycin, polymyxin B + povidone-iodine5 (6.10)Gentamycin, vancomycin + povidone-iodine4 (4.88)Cefazolin, gentamycin3 (3.66)Gentamycin, vancomycin, polymyxin B2 (2.44)Gentamycin, polymyxin B + povidone-iodine2 (2.44)Gentamycin + povidone-iodine2 (2.44)Cefazolin2 (2.44)Gentamycin2 (2.44)Cefazolin, gentamycin, polymyxin B1 (1.22)Bold values indicate statistical significance.


## 3.4. Surgical Complications

Complications are displayed in Table6. The overall complication rate was 9.84%, with no difference between groups (9.88% versus 9.76%; p=0.952). Average implant infection and cellulitis rates were 7.1% and 3.5%, respectively, with no significant difference before and after recall (p>0.05). Other complications included seroma in 2.0% of patients, hematoma in 1.2% of patients, and delayed healing in 0.8% of patients, with no differences between groups (p=0.329). Average follow-up period was 357.1 days (SD: 307.6) before recall and 168.5 days (SD: 119.0) after recall (p<0.001).Table 6
Pre- and post-recall outcomes.
Total (n = 254)Pre-recall (n = 172)Post-recall (n = 82)p valueComplicationsAny complication25 (9.84)17 (9.88)8 (9.76)0.952Infection18 (7.09)11 (6.40)7 (8.54)0.551Cellulitis9 (3.54)6 (3.49)3 (3.66)0.959Other complications10 (3.94)6 (3.49)4 (4.88)0.329Seroma5 (1.97)2 (1.16)3 (3.66)Hematoma3 (1.18)2 (1.16)1 (1.22)Delayed healing2 (0.79)2 (1.16)0 (0.00)Follow-up period, days296.22 ± 276.23357.10 ± 307.64168.51 ± 118.96<0.001Bold values indicate statistical significance.Table7 reveals complication rates specific to cases that utilized the gold standard triple-antibiotic irrigation solution before recall (bacitracin, cefazolin, gentamycin + povidone-iodine) and double-antibiotic solution after recall (cefazolin, gentamycin + povidone-iodine). There was no difference between pre- and post-recall cohorts in overall complication rate (16.38% versus 10.17%; p=0267) or infection rates (5.17% versus 8.47%; p=0.395). There was a significant decrease in other complications, including seroma, hematoma, and delayed healing (11.21% versus 1.69%; p=0.028) after the recall.Table 7
Complication rates with gold standard antibiotic combinations∗.
Total (n = 175)Pre-recall (n = 116)Post-recall (n = 59)p valueComplicationsAny complication25 (14.29)19 (16.38)6 (10.17)0.267Infection11 (6.29)6 (5.17)5 (8.47)0.395Cellulitis5 (2.86)4 (3.45)1 (1.69)0.510Other Complications14 (8.00)13 (11.21)1 (1.69)0.028∗Gold standard antibiotic combinations indicate the use of bacitracin + cefazolin + gentamycin with povidone-iodine before recall, and cefazolin + gentamycin with povidone-iodine after recall. Bold values indicate statistical significance.Patient and surgical factors were analyzed for association with complications in Table8. Patient history of smoking, breast radiation, and increased surgical time was associated with the development of “any complication” (p<0.05). Implant infection was associated with patient history of smoking, no history of prior prosthetic device, and increased surgical time (p>0.05). Cellulitis was associated with longer surgical time (0.044). Table 9 sub-stratified patient populations into smaller, more homogenous groups based on surgery type, history of radiation, use of ADM, prior prosthetic device, and reconstructive timing. With the exception of fewer overall complications in the cohort of patients with prior implant or TE after the recall (16.31% versus 3.39%; p=0.012), there was no change in complication rates after the recall in any patient subpopulation (p<0.001).Table 8
Outcomes by patient and surgical factors.
ComplicationYesNop valueAny complication (n = 25)Age54.64 ± 13.3551.56 ± 12.100.234BMI27.96 ± 5.9225.99 ± 4.780.059CCI1.60 ± 0.871.48 ± 1.010.555Smoking historyNever smoker16 (64.00)169 (74.45)<0.001Former smoker6 (24.00)57 (25.11)Current smoker3 (12.00)1 (0.44)History of breast radiation therapy8 (32.00)33 (14.54)0.025History of capsular contracture5 (20.00)25 (11.01)0.188Prior prosthetic deviceTissue expander6 (24.00)62 (27.31)0.053Implant9 (36.00)121 (53.30)None10 (40.00)44 (19.38)Surgery typeAugmentation0 (0.00)17 (7.49)0.157Reconstruction25 (100.00)210 (92.51)Total surgical time186.96 ± 97.68124.25 ± 58.96<0.001Implant volume498.20 ± 140.76441.78 ± 142.940.062Implant surgical planePre-Pectoral24 (96.00)205 (90.31)0.348Retro-pectoral1 (4.00)22 (9.69)Use of acellular dermal matrix17 (68.00)124 (54.63)0.201Number of antibiotics2.44 ± 0.652.57 ± 0.570.294Povidone-iodine 10%20 (80.00)194 (95.46)0.469Infection (n = 18)Age54.58 ± 14.9351.62 ± 11.980.322BMI28.48 ± 6.0425.96 ± 4.810.037CCI1.56 ± 0.861.47 ± 1.010.728Smoking historyNever smoker10 (55.56)177 (75.00)<0.001Former smoker5 (27.78)58 (24.58)Current smoker3 (16.67)1 (0.42)History of breast radiation therapy5 (27.78)36 (15.25)0.164History of capsular contracture2 (1.11)30 (12.71)0.844Prior prosthetic deviceTissue expander4 (22.22)64 (27.12)0.007Implant5 (27.78)127 (53.81)None9 (50.00)45 (19.07)Surgery typeAugmentation0 (0.00)17 (7.20)0.238Reconstruction18 (100.00)219 (92.80)Total surgical time174.72 ± 87.97126.70 ± 63.180.003Implant volume510.56 ± 120.26443.43 ± 143.870.055Implant surgical planePre-pectoral17 (94.44)214 (90.68)0.591Retro-pectoral1 (5.56)22 (9.32)Use of acellular dermal matrix12 (66.67)129 (54.66)0.323Number of antibiotics2.33 ± 0.692.57 ± 0.570.098Povidone-iodine 10%14 (37.84)202 (93.09)0.370Cellulitis (n = 9)Age52.94 ± 13.3551.79 ± 12.180.781BMI23.85 ± 2.6426.22 ± 4.990.157CCI1.33 ± 1.001.48 ± 1.000.663Smoking historyNever smoker6 (66.67)181 (73.88)0.786Former smoker3 (33.33)60 (24.49)Current smoker0 (0.00)4 (1.63)History of breast radiation therapy3 (33.33)38 (15.51)0.153History of capsular contracture2 (22.22)30 (12.24)0.376Prior prosthetic deviceTissue expander1 (1.11)67 (27.35)0.191Implant4 (4.44)128 (52.24)None4 (4.44)50 (20.41)Surgery typeAugmentation0 (0.00)17 (6.94)0.413Reconstruction9 (100.00)228 (93.06)Total surgical time173.67 ± 85.31128.51 ± 65.050.044Implant volume477.78 ± 155.85447.10 ± 142.910.529Implant surgical planePre-pectoral9 (100.00)222 (90.61)0.335Retro-pectoral0 (0.00)23 (9.39)Use of acellular dermal matrix5 (55.56)136 (55.51)0.998Number of antibiotics2.56 ± 0.532.55 ± 0.580.982Povidone-iodine 10%8 (88.89)208 (84.90)0.742BMI: body mass index, CCI: Charlson comorbidity index. Bold values indicate statistical significance.Table 9
Sub-stratification of case outcomes.
TotalPre-recallPost-recallp valueSurgery typeReconstructiven = 237n = 162n = 75Number of antibiotics2.53 ± 0.592.79 ± 0.481.97 ± 0.37<0.001ComplicationsAny complication37 (15.62)28 (17.28)9 (12.00)0.297Infection18 (7.59)11 (6.79)7 (9.33)0.492Cellulitis9 (3.80)6 (3.70)3 (4.00)0.912Other complications10 (4.22)6 (3.70)4 (5.33)0.562Augmentationn = 17n = 10n = 7Number of antibiotics2.82 ± 0.393.00 ± 02.57 ± 0.530.103ComplicationsAny complication0 (0.00)0 (0.00)0 (0.00)1.0Infection0 (0.00)0 (0.00)0 (0.00)1.0Cellulitis0 (0.00)0 (0.00)0 (0.00)1.0Other complications0 (0.00)0 (0.00)0 (0.00)1.0History of breast radiationPrior RTn = 34n = 26n = 8Number of antibiotics2.65 ± 0.492.84 ± 0.382.00 ± 0.00<0.001ComplicationsAny complication12 (35.29)11 (42.31)1 (12.50)0.123Infection4 (11.76)3 (11.54)1 (12.50)0.941Cellulitis2 (5.88)2 (7.69)0 (0.00)0.419Other complications3 (8.82)3 (11.54)0 (0.00)0.314No prior RTn = 208n = 134n = 74Number of antibiotics2.51 ± 0.602.78 ± 0.502.03 ± 0.44<0.001ComplicationsAny complication25 (12.02)17 (12.69)8 (10.81)0.690Infection14 (6.73)8 (5.97)6 (8.11)0.556Cellulitis7 (3.37)4 (2.99)3 (4.05)0.682Other complications7 (3.37)3 (2.24)4 (5.41)0.225Use of acellular dermal matrixADM usedn = 86n = 49n = 37Number of antibiotics2.48 ± 0.552.80 ± 0.412.05 ± 040<0.001ComplicationsAny complication15 (17.44)7 (14.29)8 (21.62)0.375Infection9 (10.47)3 (6.12)6 (16.22)0.130Cellulitis5 (5.81)2 (4.08)3 (8.11)0.430Other complications6 (6.98)2 (4.08)4 (10.81)0.225ADM not usedn = 168n = 123n = 45Number of antibiotics2.59 ± 0.592.80 ± 0.492.00 ± 0.43<0.001ComplicationsAny complication22 (13.10)21 (17.07)1 ()0.012Infection9 (5.36)8 (6.50)1 ()0.275Cellulitis4 (2.38)4 (3.25)0 (0.00)0.221Other complications4 (2.38)4 (3.25)0 (0.00)0.221Reconstruction timingImmediaten = 51n = 28n = 23Number of antibiotics2.57 ± 0.502.89 ± 0.312.17 ± 0.39<0.001ComplicationsAny complication13 (25.50)6 (21.43)7 (30.43)0.463Infection10 (19.61)4 (14.29)6 (26.09)0.291Cellulitis5 (9.80)2 (7.14)3 (13.0)0.481Other complications4 (7.84)1 (3.57)3 ()0.211Delayed-immediaten = 63n = 48n = 15Number of antibiotics2.56 ± 0.622.77 ± 0.521.87 ± 0.35<0.001ComplicationsAny complication9 ()9 ()0 ()0.070Infection3 ()3 ()0 ()0.321Cellulitis0 ()0 ()0 ()1.0Other complications2 ()2 ()0 ()0.422Delayedn = 123n = 86n = 37Number of antibiotics2.50 ± 0.612.77 ± 0.501.89 ± 0.31<0.001ComplicationsAny complication15 ()13 ()2 ()0.131Infection5 ()4 ()1 ()0.616Cellulitis4 ()4 ()0 ()0.182Other complications4 ()3 ()1 ()0.822History of prosthetic devicePrior implant or TEn = 200n = 141n = 59Number of antibiotics2.54 ± 0.602.78 ± 0.491.97 ± 0.41<0.001ComplicationsAny complication25 (12.50)23 (16.31)2 (3.39)0.012Infection9 (4.50)8 (5.67)1 (1.69)0.216Cellulitis5 (2.50)5 (3.55)0 (0.00)0.143Other complications6 (3.00)5 (3.55)1 (1.69)0.484No prior devicen = 54n = 31n = 23Number of antibiotics2.59 ± 0.502.90 ± 0.302.17 ± 0.39<0.001ComplicationsAny complication12 (2.22)5 (16.13)7 (30.43)0.211Infection9 (16.67)3 (9.68)6 (26.09)0.110Cellulitis4 (7.41)1 (3.23)3 (13.04)0.173Other complications4 (7.41)1 (3.23)3 (13.04)0.173RT: radiation therapy, ADM: acellular dermal matrix, TE: tissue expander. Bold values indicate statistical significance.


## 4. Discussion

The use of topical antibiotics intraoperatively during implant-based breast augmentation has transpired for decades [12]. However, the popularity of triple-antibiotic irrigation, particularly cefazolin, gentamycin, and bacitracin, has become a mainstream option after substantial research [4]. The recent recall of bacitracin for injection, a critical component of this triple-antibiotic recipe, disrupts this archetype and brings concern for worsening postoperative complications.This study assessed outcomes prior to and immediately after the bacitracin recall and demonstrated no detrimental impact on complication rates. Most implants placed at our institution prior to the recall were irrigated with triple-antibiotic solution in combination with povidone-iodine. Once bacitracin was removed from the irrigation protocol, there was no increase in overall complication, infection, cellulitis, or seroma rates. These results persisted when analyzing outcomes of cases that used only the gold standard triple-antibiotic combination of bacitracin, cefazolin, and gentamycin with povidone-iodine, before and after recall, as well as when patient subpopulations based on variations in surgery type and timing were analyzed for complication rates. Our early findings suggest that the recall of bacitracin from irrigation does not have a significant impact on immediate surgical outcomes, and thus alternative antibiotic and antiseptic sequences may be sufficient to provide thorough infection prophylaxis.In addition to finding analogous outcomes after the bacitracin recall, this study also identified patient and surgical risk factors that were associated with postoperative complications. Patient history of smoking was associated with higher rates of infection, a well-known risk factor for sequelae particularly in breast reconstruction [1]. Our data also revealed that lengthier surgical times were correlated with higher complication rates, including infection and cellulitis. While longer times increase exposure to pathogens, there was no difference between pre- and post-recall groups despite longer times after recall.Irrigation with triple antibiotics has become the standard of care; however, a survey of American Society of Plastic Surgery (ASPS) surgeons in 2018 found a lack of consensus with over 30 irrigation solution combinations in use [6]. Triple-antibiotic solution without povidone-iodine was favored by over 40% of members, with an additional 17% using triple-antibiotic solution with povidone-iodine [6]. Other surgeons use differing numbers of antibiotics or singularly dilute povidone-iodine solution [6]. Antibiotic selection aims to cover a broad spectrum of organisms; more than 75% of implant infections are Gram-positive and typically involve Staphylococcus aureus and Staphylococcus epidermidis; however, many are Gram-negative consisting of Pseudomonas and Escherichia coli [13]. Bacitracin was commonly used due to its low cost, broad spectrum of activity, and high potency versus Gram-positive skin flora [13]. Gentamycin has Gram-negative coverage including Pseudomonas while cefazolin is broad spectrum with good Staphylococcus coverage; thus, organisms covered by bacitracin should also be covered by the remaining two antibiotics [13]. Additionally, in vitro studies have shown that the combination of 10% povidone-iodine, gentamycin, and cefazolin is completely effective at eradicating strains of S. aureus, S. epidermidis, Pseudomonas, and E. coli [14].Prior studies of the use of these antibiotics in irrigation solution have shown major reductions in infection rates in comparison with normal saline solution [13]. Even single antibiotic solutions have protective benefits against postoperative infections and reduced rates of other complications such as seromas [15, 16]. Three antibiotics, however, may reduce infection rates substantially more. Adams et al. found infection rates less than 1% with triple-antibiotic irrigation [4]. Whether or not to combine triple-antibiotic irrigation with antiseptics such as povidone-iodine has been inconclusive as to whether it results in superior infection rates [5]. In vitro studies revealed that it reduces bacterial load by a factor of 104 to 105 for all methicillin-sensitive and resistant S. aureus and S. epidermidis strains and vancomycin-resistant Enterococcus, more effectively than triple-antibiotic solution is able to [7, 13]. Despite clinical data lacking comprehensive evidence for its combination with triple-antibiotic solution, povidone-iodine was used in more than 85% of implant cases in this study, which highlights its potential benefits in preventing infections.Capsular contracture is an intricate complication potentiated by tissue trauma, bacteria, and other sources of local inflammation; breast pocket irrigation, with or without antibiotics, is universally practiced as prophylaxis [4]. Conflicting data exists regarding the true impact of antibiotic irrigation on capsular contracture. A study by Giordano et al. found that triple-antibiotic irrigation plus povidone-iodine resulted in a capsular contracture rate of 0.6% in comparison to 6.0% without irrigation [17]. Another study found the rate of grade III-IV capsular contracture to be only 1.8% with triple-antibiotic solution [4]. These findings were opposed by a systematic review by Samargandi et al., which identified only one randomized controlled trial and a few non-randomized studies that provided weak evidence for antibiotic irrigation as contracture prevention [18]. Despite the limited evidence, it is outweighed by the benefits of infection prevention and therefore is used regularly in implant surgery [19]. Although this study did not have sufficient follow-up to perform a true analysis of capsular contracture rates and their relationship to operative antibiotic solutions, future studies should investigate this dynamic.Strengths of this study lie in its design as a regression discontinuity quasi-experiment. Regression discontinuity design allows patients to be assigned to intervention versus control groups based on falling above or below an arbitrary cutoff, in this case the date of bacitracin for injection recall [11]. Data on each side of the discontinuation are otherwise similar; there is no crossover of treatments nor nonrandom attrition of patients, and behavioral phenomena occur equally on both sides [11]. Patient cohorts were similar before and after recall in terms of surgery types, comorbidities, reconstruction timing, history of radiation or capsular contracture, and even incisional approach, as inframammary and transverse incisions have lower rates of infection in general in comparison with periareolar incisions [3].Despite these advantages, this study is limited overall by its sample size and follow-up period. Though all cases involved implant-based breast surgery, there were variations in reconstructive timing, use of ADM, and prior prosthetic device use that introduce confounding factors; our sub-analyses of our patient population suggest consistent results before and after recall in these groups; however, larger studies of these individual cohorts will need to be pursued to fully understand the impact of the recall. There was also a substantially shorter follow-up period after recall, being likely the result of the temporal change in bacitracin use in combination with environmental factors. Briefly after the bacitracin recall, the COVID-19 pandemic started in March 2020, which significantly altered patient care towards virtual visits; patients may have avoided returning for follow-up, and those that engaged in telemedicine may not have caught early findings of various complications [20]. Additionally, while the bacitracin recall was the only major change in surgical protocols, causal inference in regression discontinuity study designs may be impacted by nonrandom manipulation around the treatment cutoff, such the COVID-19 pandemic [11].Optimizing outcomes after breast implant surgery will call for larger studies to assess different antibiotic and antiseptic combinations, as the gold standard recipe with bacitracin is no longer an option. This also allows us to reevaluate antibiotic use, so that it is used judiciously without unnecessary additives, preventing the spread of drug resistance among pathogens [9]. Among the antibiotics used, Gram-positive and Gram-negative coverage must be achieved, as with cefazolin and gentamycin alone [13]. This study provides reassurance that bacitracin in triple-antibiotic solutions may not have been the keystone antibiotic required to quell most complications. Additional investigation of the long-term development of capsular contracture before and after recall, however, is necessary to fully elucidate the impact of the recall. Further, the consistent inclusion of povidone-iodine should be explored. After the 2000 moratorium on povidone-iodine by the FDA out of concern for silicone degradation, triple-antibiotic irrigation without antiseptics became the model [7]. After its return to irrigation in 2017, a large segment of surgeons still favored antibiotic solution without povidone-iodine [6, 13]. Its use as a primary irrigation should be reexplored given the known prophylactic effects on infection rates.


## 5. Conclusions

The recall of bacitracin for injection from use in intraoperative irrigation in January 2020 did not lead to worsened immediate complication rates after implant-based breast reconstruction and augmentation. This major shift in antibiotic irrigation protocols calls for additional investigation into the gold standard of preventative pocket irrigation, as bacitracin is no longer a viable option. Continued advancements in antimicrobial stewardship, in combination with optimizing surgical techniques, will improve surgical outcomes, patient satisfaction, and long-term benefits after breast implant surgery.



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