Perioperative Antibiotic Prophylaxis

Indications and Modalities for the Prevention of Postoperative Wound Infection

Background: Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality.

Method: This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines.

Results: The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance.

Conclusion: The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.

Postoperative surgical site infections (SSIs) are serious and often preventable complications that increase patient morbidity and mortality and constitute a major financial burden for the health-care system (1, 2). The evidence shows that perioperative antibiotic prophylaxis (PAP) is one of many easily implementable measures that can lower the rate of SSI. This article focuses on intravenous perioperative antibiotic prophylaxis for surgical procedures. Special aspects of peri-interventional antibiotic prophylaxis, e.g., in the context of endoscopic interventions, are addressed in the German S3 guideline on perioperative and periinterventional antibiotic prophylaxis, now in preparation. For more information on oral antibiotic prophylaxis, e.g., before gastrointestinal procedures, the reader is referred to the S3 guideline on the perioperative management of gastrointestinal tumors (POMGAT), which was published in November 2023 (3).

Learning objectives

This article should enable the reader to:

• know the epidemiology and risk factors of SSI and the measures that can be taken to prevent it,
• evaluate the indications for perioperative antibiotic prophylaxis, know the more commonly used drugs, and be acquainted with certain special situations, and
• know the modalities and indicators for the correct implementation of intravenous PAP.

Epidemiology

The findings of the 2016 national point-prevalence survey on nosocomial infection and antibiotic use in German acute-care hospitals were published in the Deutsches Ärzteblatt in 2017. The prevalence of nosocomial infection was 4.6%. SSI accounted for ca. 22% of the total; every year, approximately 1% of persons undergoing surgery as inpatients (nearly 200,000 patients) sustain an SSI (1). If only surgical interventions are considered, SSIs are found to account for more than 40% of nosocomial infections. The survey also revealed that more than 50 % of PAP was accounted for by perioperative “prophylaxis” that was given for a prolonged period without any underlying scientific evidence. If antibiotics were not used in this way, total antibiotic use in the inpatient sector would be 10–20% lower. In another study, data were analyzed from almost 5 million patients who were treated in 79 German hospitals from 2010 to 2016 (2). An SSI was documented in 10,807 of 221,113 patients (4.9%).

Some types of surgery (e.g., colorectal surgery (8.4%) versus hip replacement (4.3%), p < 0.001) were found to be associated with a significantly higher SSI rate (the quotient of SSIs to the total number of operatioⁿs). Further factors associated with a higher SSI rate (without adjustment) were obesity (defined as BMI > 30 kg/m2) and immunosuppression (relative risk [RR], 1.35 [1.28; 1.41] and 3.29 [2.99; 3.62], respectively).

SSI was associated with higher mortality (9.3% vs. 4.5%, p < 0.001), longer hospital stays (28 vs. 12 days, p < 0.001), and higher cost per case (19,008 versus 9,040 euros, p < 0.001). The mean underfunding per case was 1,534 euros. The psychological consequences for patients, some of whom must live with an open wound for a long time and endure social isolation and emotional trauma, are an intangible burden that has yet to be adequately studied.

SSI rates range from under 1% (e.g., for hip arthroplasty) to over 15% (e.g., for open pancreatic surgery), depending on the type of procedure and the patient’s risk factors. Moreover, many postoperative wound infections only arise after discharge from the hospital. In a meta-analysis, 141,347 pooled wound infections that occurred after 1,432,293 operations were evaluated: 84,984 (60.1%) of them arose after discharge (4).

Definition and risk factors

In the 1970s, the U.S. Centers for Disease Control and Prevention (CDC) introduced definitions of three classes of SSI that are still in use in nearly all surveillance systems and publications worldwide. These three classes are (5):

• superficial SSI (cutis, subcutis; A1),
• deep SSI (muscle, fascia; A2), and
• wound infections in internal organs or body cavities (A3).

The causes of postoperative wound infection are multiple and complex, involving both patient-related and pre-, intra- and postoperative surgical factors. A comprehensive presentation of risk factors for SSI is found in (6) and (7); see also the Box accompanying this article. The list makes it clear that SSI prevention is a multidisciplinary task that extends beyond the operation itself and certainly is not restricted to the administration of antibiotics.

Box

Selected risk factors for postoperative wound infection

The evidence-based prevention of wound infection

To prevent postoperative wound infection, patient management should be protocol-defined, in accordance with evidence-based measures and recommendations. The WHO recommendations on the prevention of postoperative wound infection, published in 2016 (5), were intended as a concise summary of a wide range of measures. The German Commission for Hospital Hygiene and Infection Prevention (KRINKO) has also published recommendations for the prevention of postoperative wound infection (8). Table 1 contains a listing of individual measures for the prevention of SSI that are supported by evidence of the highest level, according to a recent review (9) of meta-analyses, systematic reviews and Cochrane reviews that appeared after the WHO recommendations were published in 2016 (10, 11, 12, 13, 14, 15), as well as a further meta-analysis (16).

Table 1

A selection of evidence-based measures for the prevention of postoperative wound infection

Perioperative antibiotic prophylaxis (PAP)

Perioperative antibiotic prophylaxis consists of the short-term, usually single-shot administration of an antibiotic to prevent wound infections caused by bacteria that are either already present at the surgical site or enter it during the operation. In view of the very wide variety of surgical procedures that can be performed, the indications for antibiotic prophylaxis and the specific drugs to be used cannot be presented here with specific reference to each type of procedure. For information of this type, the reader is referred to the American guideline (17). The fundamental considerations are explained in what follows; these should be individually adapted to the operation in question, and to the risk profile of the patient.

Indication

According to a common classification that has been in use for decades (5), surgical interventions are classified as:

• clean (the incision is not exposed to inflammation, there is no opening of the respiratory, gastrointestinal or urogenital tract, and the operation is performed under aseptic conditions; SSI rates generally < 1%);
• clean-contaminated (opening of the respiratory, gastrointestinal, or urogenital tract, with no more than a small amount of leakage of contaminated fluid; SSI rates of 1% to ca. 10%);
• contaminated (the incision is exposed to acute inflammation but not purulent secretion, or there is visible contamination of the wound, or opening of the respiratory, gastrointestinal or urogenital tract, or leakage of significant amounts of contaminated fluid, or open injuries treated within four hours; SSI rates above 10% and up to 40 %);
• dirty (presence of pus, or surgery for hollow organ perforation, or open injuries not treated for more than 4 hours; SSI rates above 40%).

PAP is generally indicated for clean-contaminated or contaminated operations because of their high SSI rates (17). Antibiotic administration in dirty procedures, where an infection is already present during surgery, should be regarded as antibiotic therapy, rather than prophylaxis. Clean procedures in which no alloplastic material is implanted and without patient-related risk factors generally do not require PAP (17). PAP may be justified for a clean procedure in the presence of multiple patient-related risk factors. The same applies to clean procedures in which alloplastic material is implanted, because an SSI, if it arises, may necessitate removal of the implant, with very serious consequences for the patient. For emergency procedures and reoperations, PAP is generally indicated. Table 3 contains suggested indications for PAP with examples based on international recommendations (5, 6, 7, 8, 9). These must be adapted to the individual type of operation and are not meant to apply unchanged to all surgical procedures.

Table 2

Proposed indications for perioperative antibiotic prophylaxis depending on the procedure category

Table 3

Selected typical procedure-specific pathogens of postoperative wound infection

The choice of antibiotic

For each type of surgical procedure, there are typical pathogens that can cause an SSI (Table 3). The physician taking the patient’s history should pay special attention to potential antibiotic allergies, despite the rarity of IgE-mediated penicillin allergy (which is present in only ca. 2% of patients who state that they are allergic to penicillin) and of cross-reactivity to cephalosporins (< 5%) (18). In general, basic drugs should be used if possible. For example, cefazolin, a first-generation cephalosporin, is recommended for prophylaxis before surgical procedures in which SSIs are likely to be caused by Gram-positive pathogens that normally reside in the skin (e.g., Staphylococcus aureus, Streptococcus spp.). In operations where SSIs are likely to be caused by Enterobacterales or anaerobes (e.g., colorectal surgery), a combination of a second-generation cephalosporin (e.g., cefuroxime) with metronidazole is recommended. Drugs with a cumbersome mode of administration (e.g., slow infusion over two hours) and/or poor tissue penetration (e.g., vancomycin) should be avoided if possible. Similarly, very broad-spectrum antibiotics such as meropenem are appropriate for the empirical treatment of severe infection but should not be used routinely for PAP. Some exceptions are listed below under “targeted prophylaxis.”

The following factors should enter into the choice of the antibiotic:

• medical history (including allergies)
• type of surgical procedure
• expected or preoperatively detected pathogen spectrum
• local resistance situation
• recommendations of local guidelines
• pharmacokinetics (in particular, tissue penetration)
• potential adverse effects and toxicity

Antibiotics that can be recommended for specific procedures are listed in (17).

PAP in special situations

PAP in patients over age 65

Patients over age 65 with and SSI have a threefold higher mortality than those under age 65 (12.6% vs. 4.4%) SSI (19). In a review, special features were identified (19), including nasal screening and decolonization for Staphylococcus aureus with mupirocin and chlorhexidine before cardiac and orthopedic/trauma surgical procedures, creatinine clearance measurement before major operations lasting more than three hours, the avoidance of fluoroquinolones and aminoglycosides for PAP, and very strict adherence to the principle of terminating PAP when the procedure is over (93% of patients who die of a Clostridioides difficile infection are over age 65).

Adaptation of PAP in morbidly obese patients

Unfortunately, there are no RCTs on the topic of PAP in morbid obesity. Edmiston et al (20) gave patients 2 g of cefazolin before Roux-en-Y bypass surgery and determined serum and tissue concentrations as a function of BMI. The percentage of patients with therapeutic tissue concentrations above the minimum inhibitory concentration (MIC) was only 48.1% among patients whose BMI was between 40 and 50 kg/m², and even lower in more severely obese patients: 28.6% for BMI 50–60 kg/m², and 10.2% for BMI > 60 kg/m². This implies that the dose of PAP should be higher in patients with higher BMI, although the optimal doses remain unclear. Chopra et al. (21) recommend 2 g of cefazolin for patients with BMI 30–50 kg/m² and 3 g of cefazolin for those whose BMI exceeds 50 kg/m². Data of a high evidence level are unavailable (22).

Targeted prophylaxis in pancreatic surgery

Targeted prophylaxis is defined as specifically adapted PAP for patients with a known pathogen spectrum that has been determined by culture before surgery, e.g., of specimens taken during endoscopic retrograde cholangiopancreatography for bile drainage in patients with common bile duct stenosis. Multiple studies have been carried out to compare targeted PAP with standard PAP with respect to SSI rates and pathogens cultured from infected surgical wounds after pancreatic surgery. Seven of them (four prospective observational studies, two retrospective studies, one RCT) with a total of 849 patients who had undergone pancreaticoduodenectomy were included in a meta-analysis (23). Enterokokkus spp. was the most commonly detected pathogen. The SSI rate was significantly lower after targeted PAP than after standard PAP (21.1 % vs. 41.9 %; RR 0.55, [0.37; 0.81]). This effect was even more pronounced when only studies were considered in which there were comparable numbers of patients who had undergone preoperative biliary drainage (RR 0.45, [0.35; 0.59]). If cholangiitis is found intraoperatively, antibiotics are indicated, but this, by definition, is treatment, rather than prophylaxis. In a recently published RCT, a lower SSI rate was found when piperacillin/tazobactam was used generally in pancreatic surgery, compared to a reference group treated with cefoxitin (24). The primary endpoint, SSI at 30 days, was reached by fewer patients in the former than in the latter group (19.8% vs. 32.8%; –13.0 percentage points [-19.1%; –6.9%]; p < 0.001).

Targeted prophylaxis for multidrug-resistant Gram-negative pathogens

Multidrug-resistant Gram-negative (MRGN) bacteria are an increasing problem in Germany and around the world. For a long time, only limited data were available on the effects of MRGN-adapted PAP on ESBL-producing Enterobacterales that are detectable preoperatively by rectal screening. The WHO and KRINKO recommendations therefore contain no clear information on this point. Recently, however, a prospective, non-randomized before-and-after study (25) compared 247 patients with documented colonization by ESBL-producing Enterobacterales who received cephalosporin-based PAP with 221 who received ertapenem-based PAP: the overall SSI rates differed significantly, with 22.7 % in the cefuroxime/metronidazole group vs. 15.8 % in the ertapenem group (absolute risk difference –7.7 %, [-13.6 %; –0.8 %]), as did the rates of SSI due to ESBL (6.5% vs. 0.9%, absolute risk difference –5.6%, [-8.9 %; –2.3 %]). The NNT (number needed to treat) for the prevention of wound infection by ertapenem was 13. A European guideline (26) recommends preoperative rectal screening for 3MRGN Enterobacterales before colorectal and transplant surgery, with the adjustment of PAP to include ertapenem (or the like) if these are detected.

Modalities of PAP

The recommendations for specific measures (modalities) to be taken in the implementation of PAP are based on a systematic review that was commissioned by, and created with the aid of, the European Center for Disease Prevention and Control (ECDC). Five evidence-based modalities were identified, each of which can be monitored with indicators in audits or other types of surveillance (27). These measures include the following:

• regular analysis (at least once per year) of wound infection data by an antimicrobial stewardship team
• administration of PAP by the anesthesiologist
• correct timing of PAP (60 minutes to shortly before the incision)
• single-shot principle; second administration in the event of prolonged surgery or marked blood loss
• termination of PAP at the end of the operation

This combination of modalities was recommended as a five-point plan by the German Society for General and Visceral Surgery (DGAV) (28). The evidence for each of them will be presented below.

Antimicrobial stewardship teams

40 studies were considered, of which 24 were non-controlled before-and-after (NCBA) studies, 12 were observational cohort studies, 2 were CBA studies, and 2 were interrupted time series (ITS) studies (27).

These studies involved a total of over 600,000 patients. The overall evidence revealed that the formation of an interdisciplinary antibiotic stewardship team that met regularly and applied appropriate protocols significantly improved adherence to the proper administration of PAP and significantly lowered the SSI rate (r = –0.20, p = 0.004).

Administration of PAP by the anesthesiologist

In an uncontrolled before-and-after study (29), the responsibility for administering PAP was transferred to the anesthesia department. Adherence to correct timing of PAP rose from 11% to 91%, and the rate of SSI in cardiac surgery fell from 3.8 % to 1.4 %. In another study with a very similar design (30), adherence to correct timing rose from 72% to 92% (p < 0.001), and the SSI rate fell from 3.5% to 1.5% (p = 0.001).

The timing of intravenous PAP

In a meta-analysis (31), the following evidence-based conclusions were drawn from the published literature (14 observational studies on a total of approximately 53,000 patients):

• PAP administered after the incision is associated with a significantly increased rate of SSI (OR 1.89; [1.05; 3.40]).
• PAP given more than two hours before surgery is also associated with an increased SSI rate (OR 5.26; [3.29; 8.39]).

In a further study (32), multivariate logistic regression analysis revealed no differences in the frequency of SSI depending on whether the antibiotic was administered 60 minutes before, 30 minutes before, or just before the incision. In a recently published cohort study (33), however, the administration of cefuroxime as PAP 10–25 minutes before the incision was associated with a significantly lower SSI rate than its administration 30–55 minutes before the incision (adjusted odds ratio [aOR] 0.89; [0.82; 0.97]; p = 0.009).

The single-shot principle and the repeated administration of PAP in longer procedures

In its recommendations for the prevention of wound infection, published in 2016 (5), the WHO stated just as clearly as the ECDC had done a few years earlier (27) that PAP should be administered as a single shot for all procedures lasting less than three hours. A second intraoperative dose is recommended in case of major blood loss (> 2 L) or procedures whose duration exceeds the half-life of the antibiotic (rule of thumb: three hours). In a retrospective cohort study (34) with a total of 4078 patients, 180 (4.4%) developed a wound infection; the non-administration of a second intraoperative antibiotic dose in procedures that were over three hours long more than quadrupled the risk of wound infection (RR 4.61; [1.33; 15.91]).

Consequences of prolonged PAP

Prolonged PAP can lead to the development of resistance, Clostridioides difficile infection, and direct antibiotic toxicity (e.g., renal damage). A pertinent retrospective analysis (35) involved data from nearly 80,000 patients who had undergone different types of surgery: elective orthopedic surgery, cardiac surgery, vascular surgery, and colorectal surgery. The adjusted odds ratio (aOR) for reversible or irreversible renal damage rose with each additional day of PAP (cardiac procedures: 24 to 48 hr: (aOR) 1.03; [0.95; 1.12]; 48 to 72 hr: aOR, 1.22; [1.08; 1.39]; 72 hr: aOR 1.82; [1.54; 2.16]; noncardiac procedures: 24 to 48 hr: aOR 1.31; [1.21; 1.42]; 48 to 72 hr: aOR 1.72; [1.47; 2.01]; 72 hr: aOR 1.79; [1.27; 2.53]). The unadjusted number needed to harm (NNH) was 9 (24 to 48 hr of PAP), 6 (48 to 72 hr of PAP) and 4 (72 and more hours of PAP). Data on the harm caused by each additional day of antibiotic administration, with respect to adverse effects, bacterial superinfection, and the development of resistance, are presented in (36). 35 systematic reviews of 71 RCTs were included. Of a total of 23,174 patients, 20,345 were evaluated with respect to adverse effects (which arose in 19%), 5776 with respect to superinfection (which arose in 4.8%), and 2330 with respect to antibiotic resistance (which developed in 10.6%). Each day of antibiotic therapy was associated with a significant rise in adverse effects by 4% (OR 1.04; [1.03; 1.07]) and in severe adverse effects by 9% (OR 1.09; [1.00; 1.19]). The values for superinfection and the development of resistance were not significantly increased.

The postoperative continuation of PAP

The putative value of postoperative antibiotic prophylaxis to lessen SSI was studied in a meta-analysis of RCTs (37). The included trials covered a wide range of procedures (gastrointestinal, cardiac, thoracic, gynecological, orthopedic, maxillofacial). There were 52 RCTs, with a total of 19,273 patients, in which the continuation of PAP after surgery (varying from a single postoperative dose to five days after surgery) was compared with PAP that was terminated as soon as the procedure ended. 24 of these RCTs met so-called best practice standards, i.e., PAP was given within 60 minutes before the incision, and a repeated dose was given intraoperatively if this was indicated on the basis of the half-life of the antibiotic and the duration of the procedure. The high-quality trials did not reveal any lowering of the SSI rate with postoperatively continued PAP (RR 1.04, [0.85; 1.27]). The heterogeneity of the studies was low (I2 < 0.1%). The Figure depicts the timing of PAP during an operation (modified from [38]). Key publications on PAP with the most important findings are summarized in Table 4.

Figure

Timeline for the proper implementation of perioperative antibiotic prophylaxis (PAP)

Table 4

Synopsis of important publications on SSI prevention and perioperative antibiotic prophylaxis

Overview

The prevention of SSI is a multidisciplinary task that should include evidence-based bundles of measures. PAP that is administered properly for correct indications significantly lowers the risk of wound infection after many types of surgical procedure. On the other hand, improperly administered antibiotic prophylaxis, and especially prophylaxis that is continued after surgery, can have major deleterious effects without lowering the SSI rate any further; these include bacterial superinfection, acute toxicity, the development of resistance, and increased cost to the health-care system.

Conflict of interest statement
CE is head of the working group on general and visceral surgical infection of the German Society for General and Visceral Surgery and received an honorarium for a podcast from Infectopharm.

AB is a co-opted member of the Executive Committee of the BDA (Professional Association of German Anesthesiologists) for the area of intensive care medicine.

MP received an honorarium for a podcast from Infectopharm.

JR and SJSA declare that no conflict of interest exists.

Manuscript received on 19 October 2023, revised version accepted on 19 February 2024.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Christian Eckmann

Klinik für Allgemein-, Viszeral- und Thoraxchirurgie und ABS-Team

Klinikum Hannoversch Münden

Vogelsang 105

34346 Hannoversch Münden, Germany

Cite this as:
Eckmann C, Aghdassi SJS, Brinkmann A, Pletz M, Rademacher J: Perioperative antibiotic prophylaxis—indications and modalities for the prevention of postoperative wound infection. Dtsch Arztebl Int 2024; 121: 233–42. DOI: 10.3238/arztebl.m2024.0037

References

1. Behnke M, Aghdassi SJ, Hansen S, Peña Diaz LA, Gastmeier P, Piening B: The prevalence of nosocomial infection and antibiotic use in German hospitals. Dtsch Arztebl Int 2017; 114: 851–7

2. Eckmann C, Kramer A, Assadian O, et al.: Clinical and economic burden of surgical site infections in inpatient care in Germany: a retrospective, cross-sectional analysis from 79 hospitals. PLOS One 2022; 17: e0275970

3. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Perioperatives Management bei gastrointestinalen Tumoren (POMGAT), Langversion 1.0, 2023, AWMF-Registernummer: 088–010OL www.leitlinienprogramm-onkologie.de/leitlinien/perioperatives-managementbei-gastrointestinalen-tumoren-pomgat/; (last accessed on 10 February 2024).

4. Woelber E, Schrick EJ, Gessner BD, Evans HL: Proportion of surgical site infections after hospital discharge: a systematic review. Surg Infect (Larchmt) 2016; 17: 510–9

5. Allegranzi B, Bischoff P, de Jonge S, et al.: New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis 2016; 16: e276–87

6. Maier S, Eckmann C: Perioperative Antibiotikaprophylaxe. In: Infektionen in der Allgemein- und Viszeralchirurgie. Springer Verlag, Berlin, 2021; S. 91

7. Calderwood MS, Anderson DJ, Bratzler DW, et al.: Strategies to prevent surgical site infections in acute care hospitals: 2022 Update. Infect Control Hospital Epidemiol 2023; 44: 695–720

8. Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut: Prävention postoperativer Wundinfektionen. Bundesgesundheitsbl 2018; 61: 448–73

9. Seidelman JL, Mantyh CR, Anderson DJ: Surgical site infection prevention: a review. JAMA 2023; 329: 244–52

10. Tenner J, Melen K: Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev 2021; 8: CD004122

11. Schweizer M, Perencevich E, McDanel J, et al.: Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease gram positive surgical site infections after cardiac or orthopedic surgery: systemic review and meta-analysis. BMJ 2013; 346: f2743

12. Madrid E, Urrutia G, Roque I Figuls M, et al.: Active body surface warming systems for preventing complications caused by inadvertent perioperative hypothermia in adults. Cochrane Database Syst Rev 2016; 4: CD009016

13. Wang YY, Hu SF, Ying HM, et al.: Postoperative tight glycemic control significantly reduces postoperative infection rates in patients undergoing surgery: a meta-analysis. BMC Endocr Disord 2018; 18: 42

14. Chen S, Chen JW, Guo B, Xu CC: Preoperative antisepsis with chlorhexidine versus povidone-jodine for the prevention of surgical site infection: a systematic review and meta-analysis. World J Surg 2020; 40: 1412–24

15. Zwanenburg PR, Tol BT, Obdeijn MC, Lapid O, Gans SL, Boermeester MA: Meta-analysis, meta-regression and GRADE assessment of randomized and nonrandomized studies of incisional negative pressure wound therapy versus control dressings for the prevention of postoperative wound complications. Ann Surg 2020; 272: 81–91

16. Ahmed I, Boulton AJ, Rizvi S, et al.: The use of triclosan-coated sutures to prevent surgical site infections: a systematic review and meta-analysis of the literature. BMJ Open 2019; 9: e029727

17. Bratzler DW, Dellinger EP, Olsen KM, et al.: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect 2013; 14: 73–156

18. Shenoy ES, Macy E, Rowe T, Blumenthal KG: Evaluation and management of Penicillin allergy—a review. JAMA 2019; 321: 188–99

19. Cataldo MA, Granata G, Petrosillo N: Antibacterial prophylaxis for surgical site infection in the elderly: practical application. Drugs Aging 2017; 34: 489–98

20. Edmiston CE, Krepel C, Kelly H, et al.: Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve therapeutic levels? Surgery 2004; 136: 738–47

21. Chopra T, Zhao JJ, Alangaden G, Wood MH, Kaye KS: Preventing surgical site infections after bariatric surgery: value of perioperative antibiotic regimens. Expert Rev Pharmacoecon Outcomes Res 2010; 10: 317–28

22. Fischer MI, Dias C, Stein AT, Meinhardt NG, Heineck I: Antibiotic prophylaxis in obese patients submitted to bariatric surgery: a systematic review. Acta Cirugica Brasileira 2014; 29: 209–21

23. Pham H, Chen A, Nahm CB, Lam V, Pang T, Richardson AJ: The role of targeted versus standard antibiotic prophylaxis in pancreaticoduodenectomy in reducing postoperative infectious complications—a systematic review and meta-analysis. Ann Surg 2022; 275: 315–23

24. D`Angelica MI, Ellis RJ, Liu JB, et al.: Piperacillin-Tazobactam compared with cefoxitin as antimicrobial prophylaxis for pancreatoduodenenctomy: a randomized clinical trial. JAMA 2023; 329: 1579–88

25. Nutman A, Temkin E, Harbarth S, et al.: Personalized ertapenem prophylaxis for carriers of extended-spectrum beta-lactamase-producing enterobacteriaceae undergoing colorectal surgery. Clin Infect Dis 2020; 70: 1891–7

26. Righi E, Mutters NT, Guirao X, et al.: ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery. Clin Microbiol Infect 2023; 29: 463–79

27. Zweigner J, Magiorakos AP, Haag LM, Gebhardt S, Meyer E, Gastmeier P: ECDC technical report: Systematic review and evidence-based guidance on perioperative antibiotic prophylaxis. Abrufbar unter: www.ecdc.europa.eu/en/publications-data/systematic-review-and-evidence-based-guidance-peri-operative-antibiotic (last accessed on 13 April 2023).

28. Eckmann C, Kaffarnik M, Schappacher M, Otchwemah R, Grabein B: [Multidrug resistant gram-negative bacteria: Clinical management pathway for patients undergoing elective interventions in visceral surgery]. Chirurg 2018; 89: 40–9

29. Kanter G, Connelly NR, Fitzgerald J: A system and process redesign to improve perioperative antibiotic administration. Anesth Analg 2006; 103: 1517–21

30. Trussell J, Gerkin R, Coates B, et al.: Impact of a patient care pathway protocol on surgical site infection rates in cardiothoracic surgery patients. Am J Surg 2008; 196: 883–9

31. de Jonge SW, Gans SL, Atema JJ, et al.: Timing of preoperative antibiotic prophylaxis in 54,552 patients and the risk of surgical site infection. Medicine 2017; 96: e6903

32. de Jonge SW, Boldingh QJJ, Koch AH, et al.: Timing of preoperative antibiotic prophylaxis and surgical site infection. TAPAS, an observational cohort study. Ann Surg 2021; 274: e308–14

33. Sommerstein R, Troillet N, Harbarth S, et al.: Timing of cefuroxim surgical antimicrobial prophylaxis and its association with surgical site infection. JAMA Network Open 2023; 6: e2317370

34. Kasatpibal N, Whitney JD, Dellinger EP, et al.: Failure to redose antibiotic prophylaxis in long surgery increases risk of surgical site infection. Surg Infect 2016; 17: 334–8

35. Branch-Elliman W, O’Brian W, Strymish J, et al.: Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg 2019; 154: 590–8

36. Curran J, Lo J, Leung V, et al.: Estimating daily harms: a umbrella review with individual study meta-analysis. Clin Microbiol Infect 2022; 28: 479–90

37. de Jonge SW, Boldingh QJJ, Solomkin JS, et al.: Effect of postoperative continuation of antibiotic prophylaxis on the incidence of surgical site infection: a systematic review and meta-analysis. Lancet Infect Dis 2020; 20: 1182–92

38. Eckmann C: Perioperative Antibiotikaprophylaxe—Update 2022. Z Infektionsther 2022; 43: 37–8.