What it is:Giving an antibiotic beforebacteria ever get into sterile tissue, so an infection never starts. That's fundamentally different from presumptive therapy (treating a suspected-but-unconfirmed infection) or therapeutic therapy (treating a confirmed one). If you're prophylaxing correctly, the patient never has an active infection at any point.
The core problem:Skin and mucosal flora, mainly S. aureus, get introduced into a normally sterile space during the cut. Whether that seeds an infection depends on how much bacterial load gets in, how good the patient's local defenses are, and whether there's bactericidal drug already sitting in the tissue when it happens.
What you do about it:One narrow-spectrum, cheap, well-tolerated drug (almost always cefazolin), dosed so tissue levels are already bactericidal at the first incision, redosed if the case runs long or bleeds a lot, and stopped shortly after the wound closes. Everything in this chapter is a variation on that one idea.
Every decision in surgical prophylaxis collapses to three levers: timing(is bactericidal drug present at the moment of contamination?), spectrum(does it cover what's actually going to be introduced at this specific anatomic site?), and duration(does it stop being given once the wound is closed, so you're not just breeding resistant organisms for no benefit?). If a question describes a prophylaxis regimen, check it against those three axes before anything else.
Whether a patient gets prophylaxis at all is decided by the NRC (National Research Council) wound classification, assigned intraoperatively by the surgeon based on what actually happened in the case, not by what was planned preoperatively. This one classification is the single biggest determinant of whether antibiotics are indicated.
| Class | SSI rate, no abx | SSI rate, with abx | What defines it | Antibiotics |
|---|---|---|---|---|
| Clean | 5.1% | 0.8% | Elective, no break in technique, no entry into GI/GU/biliary/respiratory tract, no acute inflammation | Not indicated unless high-risk (prosthesis implantation or a procedure where SSI carries high morbidity) |
| Clean-contaminated | 10.1% | 1.3% | Controlled entry into one of those tracts with minimal spillage, minor technique break, or a clean case done emergently | Prophylactic antibiotics indicated |
| Contaminated | 21.9% | 10.2% | Major spillage or technique break, or acute nonpurulent inflammation already present | Prophylactic antibiotics indicated |
| Dirty | N/A | N/A | Established infection: pus, abscess, necrotic tissue | Therapeuticantibiotics required, not prophylaxis |
"Dirty" is not just a worse version of "contaminated." It's a different category of drug entirely. Clean through contaminated get prophylaxis(short, narrow, stopped fast). Dirty gets a full therapeutic coursebecause there's already a real infection, not just a risk of one. Mixing these up is the classic trap.
Layered on top of wound class is the SENIC risk score(modified to include ASA physical status), which counts how many of these four factors are present: an abdominal operation, a procedure lasting more than 2 hours, a contaminated or dirty NRC class, and more than three underlying medical diagnoses. An ASA score of 3 or higher is itself a strong independent predictor of SSI.
| # SENIC risk factors | Clean | Clean-contaminated | Contaminated | Dirty |
|---|---|---|---|---|
| 0 | 1.1% | 0.6% | N/A | N/A |
| 1 | 3.9% | 2.8% | 4.5% | 6.7% |
| 2 | 8.4% | 8.4% | 8.3% | 10.9% |
| 3 | 15.8% | 17.7% | 11.0% | 18.8% |
| 4 | N/A | N/A | 23.9% | 27.4% |
Look at the spread within a single wound class: a clean case with 0 risk factors runs 1.1% SSI, but a clean case with 3 risk factors runs 15.8%, a 14-fold difference inside the "same" category. Wound classification alone undersells risk. It's why a patient's comorbidity burden and operative time matter just as much as what the surgeon calls the case.
Surgical-site infections (SSIs) are split into incisional(superficial, involving skin/subcutaneous tissue, or deep, involving fascia and muscle) and organ/space(deeper structures, like meningitis after a neuro case). Both must occur by postoperative day 30to count, except when a prosthesis was implanted, in which case the window for deep incisional or organ/space infection extends to 1 yearafter surgery.
Two sources: endogenous(the patient's own normal flora, translocated into a sterile space during the case) and exogenous(contamination introduced during the procedure itself, from the OR environment, instruments, or team). Endogenous flora is the bigger and more predictable threat, which is exactly why prophylaxis is chosen by anatomic site: you're covering whatever normally lives there.
Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus, E. coli, and Pseudomonas aeruginosaaccount for the majority of SSIs. Because S. aureusand S. epidermidisare ubiquitous skin flora, essentially every regimen in this chapter includes gram-positive coverage as its backbone, and the site-specific add-ons (anaerobic, gram-negative, GU) are what change from procedure to procedure.
Broad-spectrum antibiotics used loosely can backfire here: wiping out normal flora destabilizes the competitive balance that normally keeps things in check, letting more pathogenic organisms proliferate. This is part of why prophylaxis regimens deliberately stay narrow instead of reaching for the biggest gun available.
Anything that lowers the bacterial inoculum needed to cause infection raises risk at a given exposure: impaired host defenses, vascular occlusive disease, traumatized tissue, and any foreign body (mesh, hardware, a joint prosthesis) all mean fewer organisms are needed to start an infection. That's the biology behind why prosthetic and implant cases get prophylaxis even when technically "clean."
Get these three right and you've covered most of what's tested. Get any one wrong and the regimen doesn't work, no matter how well-chosen the drug is.
Drug must be at the surgical site beforethe incision.
Cover the organisms actually native to that anatomic site.
Bactericidal levels maintained for the case, then stop.
The goal is bactericidal tissue concentrations already present when the incision is made, not just "given at some point before surgery." A dose given 3 hours preop, or one that shows up as a written order for "on-call to OR" and gets missed in the chaos of transport, both fail this pillar even though a dose was technically ordered. Timing errors are the single most common and most preventable cause of prophylaxis failure.
Four things drive the choice: the type of procedure, the organisms realistically expected there, the drug's own safety/efficacy/cost profile, and what the literature actually supports. In practice this converges on a short list of agents used over and over.
Cefazolinis the first-line choice for most clean and many clean-contaminated procedures. It's a first-generation cephalosporin with reliable gram-positive coverage against S. aureusand S. epidermidis, it's cheap, well-tolerated, and it's been studied more than anything else on this list. Parenteral dosing is preferred over oral across the board because IV administration reliably achieves adequate tissue concentrations, which oral absorption can't guarantee in a fasting, anesthetized, potentially hemodynamically unstable patient.
Antianaerobic cephalosporins(cefoxitin, cefotetan) step in when a case needs broader gram-negative and anaerobic coverage on top of the gram-positive backbone, classically GI tract cases where colonic flora is in play.
Ceftriaxone and other third-generation cephalosporins look appealing on paper (broader gram-negative coverage, long half-life letting you get away with fewer doses), but they're generally notpreferred for routine prophylaxis. Their gram-positive and anaerobic activity is actually worse than cefazolin's, and they cost more. If a question offers ceftriaxone as the "obviously better, broader" answer for routine prophylaxis, that's usually the distractor. (Exception: TIPS procedures, where ceftriaxone's longer coverage and gram-negative/anaerobic spectrum specifically fit.)
Vancomycinis reserved, not routine. It's justified for prosthetic device implantation at an institution with a high MRSA prevalence, or in a patient with known MRSA colonization. It should notbecome the default just because it's broader; overuse drives resistance and it's inferior to cefazolin against MSSA. If MRSA risk is low but the patient has a true β-lactam hypersensitivity, clindamycinis the substitute for cefazolin, specifically chosen to avoid reaching for vancomycin unnecessarily.
β-lactam allergy + low MRSA risk → clindamycin. β-lactam allergy + high MRSA risk, or known MRSA colonization, or prosthetic implant at a high-MRSA institution → vancomycin. No allergy → cefazolin, full stop, in almost every category of surgery in this chapter.
This is the master reference table. Every row follows the same logic: match the likely flora at that site, dose enough to cover the patient's weight, and redose if the case runs long. IA= strongly recommended, high-quality evidence. IB= strongly recommended, weaker evidence base but strong theoretical rationale.
| Procedure | Likely pathogens | Regimen | Key comment |
|---|---|---|---|
| GI Surgery | |||
| Gastroduodenal | Enteric GNR, gram-positive cocci, oral anaerobes | Cefazolin 1 g ×1 | High-risk patients only: obstruction, hemorrhage, malignancy, acid suppression, morbid obesity |
| Bariatric | Same as above | Cefazolin 2 g ×1 | Redose intraoperatively if case runs >4 h |
| Cholecystectomy | Enteric GNR, anaerobes | Cefazolin 1 g ×1 (high-risk only); laparoscopic is controversial | High-risk = open biliary procedure, acute cholecystitis, common duct stones, prior biliary surgery, jaundice, age >60, obesity, diabetes |
| TIPS | Enteric GNR, anaerobes | Ceftriaxone 1 g ×1 | Longer-acting cephalosporin preferred here specifically |
| Appendectomy | Enteric GNR, anaerobes | Cefoxitin or cefotetan 1 g ×1, orcefazolin 1 g + metronidazole 1 g ×1 | Second dose of cefoxitin if case >3 h |
| Colorectal | Enteric GNR, anaerobes | Oral: neomycin 1 g + erythromycin base 1 g at 1, 2, 11 pm the day before, plus mechanical bowel prep. IV: cefoxitin or cefotetan 1 g ×1 | Combination oral+IV beats either alone. Mechanical bowel prep is widely used but its actual benefit is debated |
| GI endoscopy (high-risk only) | Enteric GNR, gram-positive cocci, oral anaerobes | Oral amoxicillin 2 g ×1, or IV ampicillin 2 g or cefazolin 1 g ×1 | Only for high-risk patients undergoing high-risk procedures |
| Urologic Surgery | |||
| TURP, shock-wave lithotripsy, ureteroscopy | E. coli | Ciprofloxacin 500 mg PO, or TMP-SMX 1 DS tab | Positive preop urine culture = full treatment course, not just prophylaxis |
| Catheter removal, cystography, urodynamics, simple cystourethroscopy | E. coli | Same as above | Only if the patient has additional risk factors |
| Gynecologic Surgery | |||
| Cesarean section | Enteric GNR, anaerobes, GBS, enterococci | Cefazolin 1 g ×1 (<80 kg) or 2 g ×1 (≥80 kg); add azithromycin 500 mg IV ×1 if nonelective | Give before incision, not after cord clamping |
| Hysterectomy, vaginal | Enteric GNR, anaerobes, GBS, enterococci | Cefazolin 2 g ×1 (3 g if >120 kg) | PCN allergy: metronidazole or doxycycline |
| Hysterectomy, abdominal | Same as above | Cefotetan 1 g ×1 or cefazolin 2 g ×1 | Metronidazole 1 g IV ×1 for PCN allergy |
| Head & Neck | |||
| Maxillofacial | S. aureus, streptococci, oral anaerobes | Cefazolin 2 g, or clindamycin 600 mg | Repeat intraop dose if case >4 h |
| Head & neck cancer resection | Same as above | Clindamycin 600 mg at induction + q8h ×2 more doses | Add gentamicin for clean-contaminated cases |
| Cardiothoracic & Vascular | |||
| Cardiac surgery | S. aureus, S. epidermidis, Corynebacterium | Cefazolin 1 g q8h × 48 h | 2 g if >80 kg. Intranasal mupirocin BID ×5 days preop if colonized with S. aureus. Vancomycin if local MRSA prevalence is high |
| Thoracic surgery | Same + enteric GNR | Cefuroxime 750 mg IV q8h × 48 h | First-gen cephalosporins considered inadequate here |
| Abdominal aorta / lower extremity vascular | S. aureus, S. epidermidis, enteric GNR | Cefazolin 1 g at induction + q8h ×2 more doses | Graft infection is rare but carries major morbidity |
| Orthopedic & Neurosurgery | |||
| Joint replacement | S. aureus, S. epidermidis | Cefazolin 1 g preop + q8h ×2 more doses | Mupirocin BID ×5 days preop if colonized. Vancomycin only for PCN allergy or high local MRSA |
| Hip fracture repair | Same as above | Cefazolin 1 g preop + q8h × 48 h | |
| Open/compound fracture | + GNR, polymicrobial | Cefazolin 1 g preop + q8h for a full presumed infectioncourse | Add gentamicin for severe open fractures |
| Craniotomy | S. aureus, S. epidermidis | Cefazolin 1 g ×1 or cefotaxime 1 g ×1 | Vancomycin 1 g IV ×1 substitutes for PCN allergy |
| Spinal surgery | Same as above | Cefazolin 1 g ×1 | |
| CSF shunt | Same as above | Cefazolin 1 g q8h ×3 doses, or ceftriaxone 2 g ×1 | Nothing outperformed cefazolin head-to-head |
Gastroduodenal risk goes up wherever gastric acid goes down.Obstruction, hemorrhage, malignancy, and acid-suppression therapy (PPIs, H2RAs) all raise gastric pH, letting bacteria overgrow a normally near-sterile stomach. That's why prophylaxis here is reserved for high-risk patients rather than every gastric case. A single dose of IV cefazolin 30 minutes preop covers most of these.
Hepatobiliary:E. coli, Klebsiella, and enterococci dominate. Single-dose cefazolin is standard; ciprofloxacin or levofloxacin substitute for β-lactam allergy in open cholecystectomy specifically. Laparoscopic cholecystectomy prophylaxis is genuinely unsettled territory: traditionally skipped, but the trial data is mixed enough that practice varies.
If active infection is found intraoperatively(perforation, gangrenous gallbladder, suppurative cholangitis), the case converts from prophylaxis to therapeutic postoperative antibiotics. This is the same wound-class logic as clean vs. dirty: what you find during the case changes the entire post-op plan.
Colorectal surgery carries the heaviest bacterial burden of any routine case, gram-negative aerobes and anaerobes predominate, with gram-positive aerobes also relevant. Risk factors worth flagging: age over 60, hypoalbuminemia, poor bowel prep, chronic corticosteroids, malignancy, and operations running past 3.5 hours.
Mechanical bowel prep(4 L of polyethylene glycol, or 90 mL of sodium phosphate, given orally the day before) is still widely used by surgeons despite evidence questioning whether it changes SSI rates at all. Know that it's controversial, not proven.
Combination oral + IV prophylaxis beats either alone.The classic oral regimen is neomycin 1 g + erythromycin base 1 g, given at three time points the day before surgery (roughly 19, 18, and 9 hours preop, often written as 1 pm, 2 pm, 11 pm). On the IV side, cefoxitin or cefotetanare the workhorses, chosen for antianaerobic activity; other 2nd- and some 3rd-generation cephalosporins also work. Cefotetan's longer half-life makes it preferable for longer operationssince a single dose covers the whole case, whereas cefoxitin may need an intraoperative redose past 3 hours.
Appendectomygets preoperative antibiotics in essentially every case, not just high-risk ones (unlike gastroduodenal surgery). Cefoxitin/cefotetan 1 g, or cefazolin 1 g plus metronidazole 1 g, both work. Postoperative antibiotics aren't needed if nothing unexpected was found; if perforation or abscess is present, that's now a therapeutic course, not prophylaxis.
As long as urine is sterile going in, SSI risk after urologic surgery is genuinely low, and the benefit of routine prophylaxis is debated for many low-risk procedures. E. coliis the dominant organism when infection does occur.
Definitely prophylax:TURP, transurethral bladder tumor resection, shock-wave lithotripsy, percutaneous renal surgery, and ureteroscopy. Ciprofloxacin 500 mg PO or TMP-SMX 1 DS tablet cover these. Lower-risk procedures(catheter removal, cystography, urodynamics, simple cystoscopy) only need prophylaxis if the patient has additional risk factors.
Abdominal-approach urologic surgery(nephrectomy, cystectomy) doesn't follow the "urologic is usually low-risk" rule. It gets treated as a clean-contaminated abdominal case instead, because the abdominal entry itself is the dominant risk, not the GU tract.
Cesarean section prophylaxis is universal, given regardless of individual risk factors, because the benefit is consistent across the board. Weight-based cefazolin dosing (1 g under 80 kg, 2 g at or above 80 kg) plus azithromycin 500 mg IV for nonelective cases. The one timing rule that's genuinely counterintuitive: give the antibiotic before the incision, not after the cord is clamped, even though the older instinct was to delay dosing to avoid drug exposure to the fetus. Current evidence favors maternal infection prevention over that theoretical fetal concern.
Vaginal hysterectomy without prophylaxis carries a genuinely high infection rate, higher than abdominal hysterectomy, which is why it's a hard recommendation regardless of risk factors: cefazolin 2 g (3 g if >120 kg), or metronidazole/doxycycline for β-lactam allergy.
Abdominal hysterectomyhas a lower baseline SSI rate than vaginal, but still gets prophylaxis in every patient: first- (cefazolin), second- (cefotetan), or third-generation cephalosporins are all acceptable choices here.
Whether prophylaxis is warranted depends heavily on whether the mucosal layer is breached. Clean procedureslike thyroidectomy or a simple tooth extraction have low SSI rates and don't need prophylaxis. Anything cutting through a mucosal layeris high risk and does.
The cefazolin dose here is unusually high (2 g) on purpose:the standard dose doesn't reliably inhibit anaerobes, but the 2-g dose produces concentrations high enough to be effective against them, which matters because oral anaerobes are part of the target flora in this region. Duration has traditionally run 24 hours in most studies, though single-dose therapy may work just as well.
For maxillofacial surgery, a single dose of clindamycin is enough unless the case runs past 4 hours, in which case give a second intraoperative dose. Head and neck cancer resection(including free-flap reconstruction) is the outlier that gets a full 24 hours of clindamycin rather than a single dose, reflecting the higher contamination risk of that surgery.
Most cardiac procedures are technically "clean," but prophylaxis still clearly lowers SSI rates, which is a useful reminder that wound class alone doesn't decide the antibiotic question. Pathogens are almost entirely skin flora: S. aureus, S. epidermidis, Corynebacterium, with gram-negative enterics only rarely involved.
Risk factors worth knowing:obesity, renal insufficiency, connective tissue disease, reexploration for bleeding, and poorly timed dosing. That last one circles back to Pillar 1: this is a specialty where timing errors are especially costly given how much is at stake with a sternal or mediastinal infection.
Cefazolin 1 g q8h for 48 hoursis standard (2 g if >80 kg), given no earlier than 60 minutes before incision and no later than induction. Extending beyond 48 hours does not lower SSI rates further, it just adds resistance pressure and cost. Intranasal mupirocintwice daily for 5 days preoperatively is added for patients known to be colonized with S. aureus. Vancomycin is reserved for high local MRSA burden or when sternal wounds may need re-exploration for possible mediastinitis.
Thoracic surgeryis the outlier: first-generation cephalosporins are considered inadequate here, so cefuroxime 750 mg IV q8h × 48 his used instead, reflecting the added enteric gram-negative risk. Shorter durations haven't been well studied for thoracic cases, unlike cardiac.
Abdominal aortic and lower-extremity vascular procedures benefit clearly from prophylaxis. Infections here are uncommon, but a graft infectionis a high-morbidity event, which is why the threshold for prophylaxis stays low even though absolute event rates are low. Twenty-four hours of IV cefazolin is standard; 24 hours of oral ciprofloxacin substitutes for β-lactam allergy.
Prophylaxis matters most here whenever prosthetic material goes in, pins, plates, artificial joints, because a foreign body drastically lowers the bacterial load needed to seed an infection (the same principle from the pathophysiology section). Pathogens mirror other clean cases: staphylococci dominate, gram-negative aerobes are infrequent.
Cefazolin is the drug of choice.Hip fracture repair and joint replacement both get 24 hours of therapy. Vancomycin is notthe default here, it's reserved for a documented β-lactam hypersensitivity or an institutional MRSA prevalence that specifically justifies it.
Open/compound fractures are treated differently in kind, not just degree:because these wounds are already contaminated by the injury itself, they're managed as a presumed infection rather than pure prophylaxis, meaning the antibiotic course runs for the duration appropriate to treating that presumed infection. Severe open fractures often need added gram-negative coverage (gentamicin) given the polymicrobial contamination risk from the traumatic wound itself.
Whether prophylaxis helps at all in neurosurgery is more debated than in most other specialties covered here. What evidence exists supports a single dose of cefazolin lowering SSI risk after craniotomy(cefotaxime 1 g is an alternative; vancomycin 1 g IV for PCN allergy). Spinal surgeryuses cefazolin 1 g as a single dose, though the trial base comparing regimens is limited. CSF shunt proceduresget either cefazolin 1 g q8h ×3 doses or ceftriaxone 2 g ×1; no agent studied has clearly beaten cefazolin head-to-head.
Bactericidal tissue levels must stay present for the entireprocedure, not just at the start. Cases running past a drug's typical redosing interval (roughly every 3-4 hours for cefazolin depending on renal function, sooner with major blood loss) need an intraoperative repeat dose. Watch for this specifically in bariatric surgery (>4 h), appendectomy/colorectal with cefoxitin (>3 h), maxillofacial (>4 h), and head/neck cancer resection.
This chapter repeatedly bumps the dose for higher-weight patients because underdosing a larger volume of distribution is a real failure mode: cefazolin 2 g instead of 1 g for cardiac and bariatric patients >80 kg, cesarean section 2 g for ≥80 kg, and vaginal hysterectomy 3 g for >120 kg. If a vignette gives you a weight, it's testing this.
Two specialties in this chapter (cardiac and joint replacement) call out intranasal mupirocin BID for 5 days preoperativelyspecifically for patients known to be colonized with S. aureus. This is a decolonization strategy layered on top of, not instead of, standard IV prophylaxis.
The general β-lactam allergy substitution logic across this whole chapter:clindamycin when MRSA risk is low, vancomycin when MRSA risk is high or a prosthesis is involved, metronidazole or doxycycline for gyn cases, and fluoroquinolones (ciprofloxacin/levofloxacin) for GU-flora-driven cases like open cholecystectomy or vascular surgery.
The chapter also frames this as a systems problem: educate staff on why timing matters, standardize ordering (protocols/preprinted order sets driven by evidence, formulary, and local resistance patterns), standardize delivery so the <1 hour preop window is actually hit reliably, and track compliance and infection rates with feedback loops. On the wards, this shows up as pharmacy order sets and time-out checklists, not just "which drug."
| Parameter | When | Watching for |
|---|---|---|
| Time of first dose relative to incision | Preoperative holding area / induction | Dose given within 60 min of incision; flag anything ordered "on-call" instead of scheduled |
| Intraoperative redosing | Every case, tracked against the drug's redosing interval | Procedures exceeding ~3-4 h (cefazolin) or with major blood loss need a repeat dose |
| Total duration of prophylaxis | From first dose to discontinuation | Most regimens: stop at or within hours of wound closure. Cardiac and orthopedic joint/hip-fracture cases: 24-48 h is the studied window, not indefinite |
| Intraoperative findings | At time of surgery | Perforation, abscess, gangrenous tissue, or suppuration converts the plan from prophylaxis to a full therapeuticcourse |
| NRC wound class assignment | Documented by surgeon at end of case | Drives postoperative antibiotic decisions and infection-control reporting |
| Renal function | Baseline, especially with vancomycin or prolonged courses | Dose/interval adjustment for renally cleared agents |
| MRSA colonization status | Preop screening in cardiac/ortho implant candidates | Triggers mupirocin decolonization protocol and possible vancomycin substitution |
Extending prophylaxis beyond the studied window doesn't lower infection rates further, the cardiac literature makes this explicit at 48 hours, but the same logic underlies why most other regimens in this chapter are single-dose or capped at 24 hours. Longer isn't safer once the wound is closed; it's just more resistance pressure, more C. diff risk, and more cost for no additional benefit.
Most of this conversation happens preoperatively, and it's short because the patient generally isn't the one making the decision, they need to understand what's happening and why.