In addition, more than 70% of the patients had a skin-sparing mastectomy. An ADM was used in 44 cases (37%), and despite being a risk factor for seromas and persistence of the use of a drainage catheter, the use of this bioprosthetic mesh did not appear to be a risk factor for early infections (P = 0.92). Similarly, initial and final expansion volumes did not predict risk of early or late TE infection (P > 0.36). Furthermore, almost 40% of the patients who developed a TE infection had developed some degree of skin flap necrosis, and 28% developed a postsurgical seroma or hematoma, requiring drainage catheter placement for an extended period.
Prophylactic Antimicrobial Regimens
All patients received a standardized perioperative systemic antimicrobial therapy; the most common drugs used were cefazolin (81%), clindamycin (6%), and ampicillin-sulbactam (4%). Thereafter at the discretion of the surgeon, more than 85% of the patients underwent subpectoral TE pocket irrigation with a broad-spectrum antimicrobial solution. The most commonly used regimen was bacitracin plus polymyxin B (66%), followed by bacitracin plus cefazolin and gentamicin (9%) and vancomycin plus ciprofloxacin (4%). After surgery, oral prophylactic antibiotics were used in 78% of cases, either for a week or until the drainage catheters were removed. The most commonly prescribed postsurgical antimicrobial drugs were cephalexin (26%), cefadroxil (22%), amoxicillin/clavulanate (8%), trimethoprim/sulfamethoxazole (6%), and clindamycin (4%).
Time to Infection and Implant Removal
Once an infection occurred, the median time from initial reconstructive surgery to infection was 47 days (range, 13–309 days, with a 25th and 75th percentile of 26 and 107 days, respectively). Overall, the median time from infection to implant removal was 4 days (range, 0–136 days, with a 25th and 75th percentile of 2 and 8 days, respectively).
Gram-positive organism infections were identified in 73% of patients, and Gram-negative infections were identified in 27% (Table 3). A polymicrobial infection was identified in 20 patients (17%). Methicillin-resistant Staphylococcus epidermidis (24%) was the most frequently encountered organism, followed by methicillin-sensitive Staphylococcus aureus (15%), Pseudomonas spp. (14%), and methicillin-resistant S. aureus (12%). The frequency of each causative microorganism remained relatively stable throughout the period studied; methicillin-resistant S. epidermidis was the most common microorganism throughout. These also remained stable when stratified by different postoperative time periods (Fig. 1). Of interest, Pseudomonas and other facultative Gram-negative rods were predominant at 30 days after surgery (accounting for 31% of TE infections), as well as at 90 days (27% of infections) and 180 days (25% of infections; Fig. 1). Furthermore, during the past 8 years of our study, the incidence of Gram-negative TE infections ranged from 24% to 44% of all TE infections (Fig. 2). Of note, similar to the proportion of patients without ADMs, of the 37 patients with an ADM, 62% had a Gram-positive infection and 35% had a Gram-negative infection with 6 (16%) had a polymicrobial infection.
Empiric Antimicrobial Regimens
Multiple empiric antimicrobial regimens were used to treat TE infections (Table 4). The most ineffective empiric regimens were categorized as narrow spectrum, such as the isolated use of vancomycin (12 cases, 10%), amoxicillin/clavulanate (10 cases, 8%), cephalexin (8 cases, 7%), or ciprofloxacin (5 cases, 4%). As a group, narrow-spectrum antimicrobial regimens with predominantly Gram-negative coverage (20 cases, 17%) were deemed appropriate in only 45% of cases, and narrow-spectrum antimicrobial regimens with predominantly Gram-positive coverage (34 cases, 29%) were appropriate in only 62% of cases. In contrast, as a group, the use of broad-spectrum antimicrobial regimens (55 cases, 47%) was considered appropriate in more than 90% of the cases in which they were used. The most commonly used regimens were the combination of vancomycin plus piperacillin and tazobactam (18 cases, 15%), vancomycin plus ciprofloxacin (9 cases, 8%), and daptomycin plus piperacillin and tazobactam (8 cases, 7%). Interestingly, we discovered that the majority of plastic surgeons were providing a narrow-spectrum empiric antibiotic regimen, compared with the infectious disease specialists whom were consulted on all of the patients in whom broad-spectrum antimicrobials were recommended.
Subsequent Breast Reconstruction
Once the infection was adequately treated, 60 patients (51%) decided to proceed with a subsequent reconstructive procedure. The median time from implant removal to subsequent reconstruction was 180 days (range, 30–1,232 days). Twenty-eight patients (47%) proceeded with an implant-based reconstruction, 22 patients (37%) underwent a flap reconstruction, and 10 patients (17%) underwent a combined implant-flap reconstructive procedure. Patients who underwent a flap reconstruction were almost equally split in terms of the type of flap; approximately one-third had an extended latissimus dorsi flap, one-third had a deep inferior epigastric perforator flap, and one-third had a muscle-sparing transverse rectus abdominis myocutaneous flap.
The rate of postoperative TE-related infections continues to remain unacceptably high despite the use of several prophylactic antimicrobial regimens. Once an infection occurs, from the very onset, it is paramount to optimize the empiric antibiotic regimen to successfully salvage the implant, decrease overall morbidity, and avoid delays in adjuvant therapy. Our results demonstrate that empiric antimicrobial regimens currently used for the treatment of TE infections are diverse and do not generally cover the spectrum of organisms that cause TE infections, including methicillin-resistant staphylococci and Gram-negative rods.
Similar to previous studies, our data show that the organisms causing TE infection and implant loss are usually resistant to commonly used postoperative prophylactic regimens that target predominantly Gram-positive bacteria, including first-generation cephalosporins.1,15,18,19 In addition, approximately two-thirds of these infections occur more than 30 days after surgery, which is often beyond when most drains have been removed and antibiotic regimens discontinued. It has been speculated that prophylactic antibiotics prevent early infections caused by nonresistant bacteria while selecting for resistant organisms that can lead to late infection.15
Consensus has not been reached on either the use of postoperative prophylactic antibiotics or the appropriate overall duration needed to prevent infections.3,18 Several studies have revealed that following Surgical Care Improvement Project guidelines in prosthetic breast reconstruction and withholding postoperative prophylactic antibiotics can increase a patient’s SSI reoperation risk 4.7 times. In addition, stopping antibiotic prophylaxis after 24 hours could raise the rate of infection requiring the removal of a TE from 7.9% to 31%.20,21 In these studies, the bacteria isolated in the groups not treated with an extended course of postoperative prophylactic antibiotics were more diverse than those seen in other studies in which patients used long-term postoperative antibiotics.15,20–23
Targeting postoperative prophylaxis to patients at high risk for infection has been suggested as an alternative to universal postoperative prophylaxis in prosthetic breast reconstruction to prevent adverse outcomes from extended use, such as increasing resistance, allergic reactions, and other infections associated with antibiotic use.15 A heightened awareness of those patients who are at an increased risk for infections including those who are obese, smokers, those with mastectomy skin necrosis, or a need for radiation therapy should be considered for prolonged use of prophylactic postoperative antibiotics.5,9,23–26
Once an SSI or TE infection is diagnosed, it is paramount to treat the infection with an empiric broad-spectrum antimicrobial regimen that will not only cover the most common causative organisms but also remain active among the organisms embedded in an early biofilm infection. Therefore, after reviewing the perioperative and postoperative antimicrobials used in our patient population, as well as the organisms responsible for TE infections, we have developed a comprehensive treatment algorithm (Fig. 3) to provide a more consistent approach to a patient presenting with a breast TE infection.27
In our algorithm, we encourage all patients to proceed with a breast ultrasound. If any periprosthetic fluid is observed, ideally the fluid should be aspirated and submitted for microbiological analysis to determine whether bacteria, fungi, or acid-fast bacilli is present.28,29 In the meantime, while awaiting culture results, and after reviewing the patient’s medication and allergy profile, including any antimicrobial drugs used in the patient’s perioperative and postoperative prophylactic regimen, depending on the severity of the infection, the physician should prescribe either an oral or intravenous empiric antimicrobial regimen that targets methicillin-resistant staphylococci and Gram-negative rods including Pseudomonas. Furthermore, the empiric antimicrobial regimen should favor antibiotics that are active against the bacteria embedded in the biofilm. For example, for Gram-positive coverage, oral minocycline plus rifampin or intravenous daptomycin plus rifampin should be favored over vancomycin or linezolid.30–34 For Gram-negative coverage, quinolone, such as ciprofloxacin, should be prioritized over a β-lactam antimicrobial regimen.35–39 If the culprit organism has been eventually recovered, usually within the first 48 hours, the empiric regimen should be transitioned to a specific biofilm-active antibiotic treatment regimen dictated by the microorganism’s antimicrobial susceptibility panel, and hence, the probability for antimicrobial resistance should be extremely low. Throughout this time period, to optimize patient’s care and increase the salvage rate of TE infections, based on the experience of other complex device-related infections40,41 and knowledge of broad-spectrum antimicrobial coverage and activity of antibiotics within the biofilm matrix, the assistance of an infectious diseases consultant is highly beneficial.
One limitation of our study is the retrospective nature of the data collection. Also, because the majority of our patients had an immediate reconstructive procedure, our algorithm may not apply to patients who have had a delayed reconstructive procedure. Furthermore, to avoid including patients with a noninfectious inflammatory syndrome, and confounding our results, we did not include patients whose SSIs were adequately treated with empiric antibiotics in the absence of any culture data but only included patients who had developed a “definite” TE infection that led to removal of the TE with positive intraoperative cultures. Also, we cannot comment on the potential that withholding prophylaxis would have caused a different number of infections and TE losses. Evidence from a randomized controlled trial would be required to challenge the well-established practice patterns, which are currently based on anecdotal experience rather than evidence-based data.20 In addition, because many of our patients with cancer were not health care naive and may be colonized with hospital-acquired resistant organisms, the antimicrobial trends seen in our patient population might not accurately reflect national trends in TE infections. Therefore, to validate our recommendations, we are currently planning to proceed with a prospective clinical study.
To salvage an infected breast TE, based on individual hospital epidemiological data, the most common organisms causative for TE infection should be empirically covered. At our institution, methicillin-resistant staphylococci and Gram-negative rods, including Pseudomonas, were responsible for more than 60% of all TE infections across different postoperative time periods and years of our study. Therefore, these organisms should be empirically covered by broad-spectrum antibiotics that can also act on biofilm-embedded organisms, rather than by traditional narrow-spectrum regimens such as first-generation cephalosporins alone. Once an organism has been identified, the empiric antimicrobial regimen should be transitioned to a specific biofilm-active antimicrobial regimen dictated by the microorganism’s antimicrobial susceptibility panel. Finally, to optimize the care of these patients, it is of benefit to have an infectious diseases consultant assist in the care of these complex medical device-related infections.
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Copyright © 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons. All rights reserved.
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