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Chapter 3
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Controversies inAntibiotic Prophylaxis
inOrthopaedic Surgery
ElishaKrasin
Abbreviations
HIV Human Immunodeciency Virus
VRE Vancomycin-resistant enterococci
MRSA Methicillin-resistant staphylococcus aureus
MSSA Methicillin-sensitive staphylococcus aureus
SSI Surgical site infection
THA Total hip arthroplasty
TKA Total knee arthroplasty
Introduction
Surgical site infection is a highly concerning issue in the eld of orthopaedic surgery. What starts as a simple injury that could be effectively treated with a standard
procedure can quickly escalate into a chronic condition, necessitating prolonged
hospitalisation, ongoing antibiotic therapy, and repeated surgeries. The complications associated with infection can result in treatment failure, disability, limb amputation, and even mortality. Given these implications, the prevention of infections in
orthopaedics is of paramount importance.
E. Krasin (*)
Maccabi Healthcare Services, Tel Aviv-Yafo, Israel
Switzerland AG 2024
J. Faintuch, S. Faintuch (eds.), Recent Strategies in High Risk Surgery,
https://doi.org/10.1007/978-3-031-56270-9_3
39© The Author(s), under exclusive license to Springer Nature
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E. Krasin
Early Experience
Once penicillin became available during World War II, it was used to prevent infections in orthopaedic surgery [1]. Controversy followed, when, in 1960, Pulaski and
Taylor noted that most infecting organisms in orthopaedic surgery were resistant to
the antibiotics commonly used for prophylaxis at the time. They also mentioned that
infection rates were higher among patients who received antibiotics. Their conclusion was that “routine indiscriminate antibiotic prophylaxis for elective surgical
conditions served no useful purpose” [2].
Burke pointed out in 1963 that “antibacterials can increase natural resistance
when natural mechanisms are ineffective” [3]. The contemporary practice of
perioperative antibiotic prophylaxis in orthopaedics is based on the work of
Boyd and Burke, who in 1973 investigated ways to reduce the incidence of
wound and soft tissue infections, as well as infections around orthopaedic
implants [4]. Norden in 1976 still believed that antibiotic prophylaxis was a
controversial issue [5] Originally, the decision to prescribe cephalosporins was
mainly aimed at the prevalent Staphylococcal and Streptococcal infections.
These bacteria were largely susceptible to methicillin as well as rst and second
generation cephalosporins.
The routine use of cephalosporins in orthopaedics has been proven by numerous
clinical trials, which have convincingly demonstrated their effectiveness in reducing
infection rates. Rosenfeld et al. concluded that “rst-generation cephalosporins,
such as cephalothin or cefazolin, are the best chemoprophylactic agents because of
their excellent antistaphylococcal activity and lack of signicant toxicity” [6].
Current Epidemiology and Microbiology
Most surgical site infections are obtained during the operation, with the most common source being the patient’s skin as well as airborne micro-organisms from operating theatre staff [7]. In clean orthopaedic surgery, the reported wound infection
rate is 5.1%, while the administration of preoperative antibiotics reduces it to 0.8%.
In clean- contaminated surgery the rates are 10.1% and 1.3% respectively, and in
contaminated surgery 21.9% and 10.2%, [8]. Administration of antibiotic prophylaxis in surgery of open fractures provided “a large, consistent reduction in infection
risk” [9].
Present day developments in bacterial resistance and the increasing number
of methicillin-resistant staphylococci may make the use of rst- or second-generation cephalosporins in orthopaedics almost obsolete. This contrasts with their
still fairly good acceptance in the eld of general surgery. About 30% of infections after joint replacement are polymicrobial, meaning they are a combination
of Gram-negative and Gram-positive bacteria. Of the monomicrobial infections,
3 Controversies inAntibiotic Prophylaxis inOrthopaedic Surgery
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43% are caused by Staphylococcus aureus (4% by methicillin-resistant bacteria)
[10]. Coagulase- negative Staphylococci were found to be responsible for 30% of
infections after knee replacement and 19% after hip replacement. Gram-negative
bacteria were found in 17% of infections after hip and knee arthroplasty [10].
A Spanish study of total joint arthroplasties showed an increase in Gram-negative
infections along the years, from 21% to 67%. Staphylococcus aureus remains the
most common microorganism after fracture surgery, but resistance to methicillin is
increasing and may even exceed susceptible species in some areas [10]. Coagulasenegative staphylococci are also common and 80–90% resistant to methicillin. The
incidence of multidrug-resistant Gram-negative bacteria such as Pseudomonas
aeruginosa and Acinetobacter baumannii is increasing, as is the incidence of gas-
trointestinal organisms such as Escherichia coli, Enterobacter, Enterococcus,
Klebsiella, and Proteus [10, 11].
Our recent work demonstrated an increase in oxacillin resistance of Staphylococci,
and high incidence of non-gastrointestinal Gram-negative bacteria and gastrointestinal bacteria [12]. Currently, Staphylococcus aureus resistance to vancomycin is
rare, but could become a problem in the future. Intermediate vancomycin-resistant
Staphylococcus aureus is already observed and is likely to become more of a problem in the near future [12].
41
Vancomycin-Resistant Enterococci
These are of major importance in orthopaedic surgery because of their potential to
cause infections and complications that are difcult to treat. In addition, the presence of VRE in healthcare facilities raises concerns about the potential for transmission and outbreaks among patients, particularly those with compromised immune
systems [13].
Cutibacterium acnes is considered a major pathogen in shoulder surgery and
may exceed even Staphylococci in prevalence [7]. It shows good sensitivity to antibiotics commonly used for bone and joint infections, particularly beta-lactams, quinolones, and rifampicin. However, resistance to some antibiotics, in particular
clindamycin, is emerging. Furthermore, Cutibacterium acnes, despite being an
anaerobic bacterium, also shows natural resistance to metronidazole.
Fungal Infections
These occur in less than 1% of prosthetic joint infections, but should nevertheless
be considered, if not in prophylaxis, in the diagnosis itself of the infection [14].
Precisely because of the low frequency, they tend to be overlooked and misdiagnosed, precipitating much tissue destruction and deleterious systemic effects.
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E. Krasin
General Recommendations
The optimal prophylactic antibiotic should include coverage for resistant Grampositive as well as for common Gram-negative agents. Adequate bloodstream and
tissue concentrations should be achieved along the entire procedure. Additionally, it
is crucial that bacteria do not readily develop resistance to this antibiotic, considering its intended widespread utilisation.
Practical Guidelines
The simplest way to prevent postoperative infections is not to operate, whenever
intervention is not mandatory. The indications for most orthopaedic operations are
relative and in most cases, there is a conservative alternative. In patients with low
functional requirements and increased risk for infection such as the elderly, the
immunosuppressed and those with serious comorbidities, conservative non-surgical
treatment should always be considered.
Preoperative screening and decolonisation of methicillin-resistant Staphylococcus
aureus and methicillin-sensitive Staphylococcus aureus is a controversial issue, but
most authorities recommend nasal swabs for screening in elective situations. If positive for Staphylococcus aureus, decolonisation by nasal application of mupirocin
twice daily to both nares for 5days should be considered [7]. Some recommend
additional bathing with chlorhexidine daily before scheduled surgery for 5days.
Current Practice
The adopted guidelines for perioperative antibiotic administration in orthopaedics
are quite standard, and in my opinion, they will soon be obsolete. A preliminary
distinction should be made between the prevention of infection in surgery of closed
fractures and injuries as well as clean elective or semi-elective surgery, in comparison with open fractures and injuries.
Timing andDuration
These are somewhat controversial points as well. Most authors recommend administering the rst dose about half an hour before the incision and no more than 2h
before. Administering the drug during or after the start of surgery renders treatment
ineffective [15]. The ideal duration of postoperative antibiotic treatment is not yet
clearly dened, although most reports suggest that there is no additional benet
from prophylactic antibiotic treatment more than 24h after surgery [15].
3 Controversies inAntibiotic Prophylaxis inOrthopaedic Surgery
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A study of extended oral antibiotic prophylaxis in high-risk patients involved a
7-day antibiotic regimen (Cefadroxil 500mg two times per day or Clindamycin
300mg three times per day with Sulfamethoxazole and trimethoprim 800mg/160mg
two times per day) in patients with a BMI ≥35, diabetes mellitus, smoking, chronic
kidney disease, autoimmune disease or with nasal colonisation of MSSA or
MRSA. Before the introduction of the extended antibiotic therapy protocol, the
incidence of PJI in the primary THA and TKA in the high-risk subset were 4.3%
and 2.1%, respectively. After the introduction of this protocol, the corresponding
rates decreased to 1.1% and 0.4%, which is in line with the rates observed in patients
without high risk receiving standard perioperative prophylaxis [16]. The American
Academy of Orthopaedic Surgeons (AAOS) recommends prophylaxis for no more
than 24h, regardless of the use of drains or catheters [17].
43
Closed Fractures andClean Elective or Semi-Elective Surgery
Cefazolin 2g (or 3g if >100kg body weight) IV 30–60min before skin incision,
then cefazolin 2g or 3g IV every 8h for 24h is advised. In beta-lactam allergic
patients the recommended protocol is vancomycin IV (15mg/kg) or clindamycin
600–900mg IV 60–90min before skin incision, then vancomycin every 12h or
clindamycin 600–900mg IV every 6h for 24h [8, 18].
Clostridioides Difcile
In the UK, cephalosporins are no longer rst line prophylaxis in many centres,
mainly due to concerns about Clostridioides difcile infection. Third-generation
cephalosporins are strongly associated with such supervenient infection and
prophylaxis with a single dose of cephalosporin is sufcient to cause the development of Clostridioides difcile colonisation. Flucloxacillin is a penicillinaseresistant penicillin with good coverage against Staphylococcus aureus (it is
ineffective against MRSA and 90% of coagulase-negative staphylococci) and
is commonly used in the UK as rst-line treatment for Staphylococcus aureus
infection [17].
Open Fractures
The Gustilo and Anderson classication is one of the most broadly used classications for open fractures. The incidence of wound infection is directly correlated with the class of fracture, with 0–2% in grade I fractures, 2–7% in grade II
fractures, 7–10% in grade IIIA fractures, 10–50% in grade IIIB fractures, and
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25–50% in grade IIIC fractures [19]. The efcacy of prophylactic treatment for
the types IIIB and IIIC is questionable, contrasting with types I-IIIA, for which
the benet is clear. In case of obesity of more than 100kg, the doses should be
doubled [20].
The duration of antibiotic therapy varies from one institution to another and the
choice of drugs is not standardized. Penicillins, cephalosporins, aminoglycosides
and uoroquinolones are common options. Broader spectrum agents including
monobactams and glycopeptides, have been used for additional coverage [21]. In
general, antimicrobials are discontinued 24h after surgery, but it may be appropriate to continue them for up to 72h for heavily contaminated wounds. Antibiotics
should not be given beyond 72 h unless a second surgery is performed within
that time.
Here is an example of the protocol used by Garner etal. for open fractures:
• For type I and II open fractures: Cefazolin 2 g IV immediately and q8 hours,
with three total doses.
For penicillin allergic: Clindamycin 900mg IV immediately and q8 hours (three
total doses).
• For type III open fractures: Ceftriaxone 2 g IV immediately; Vancomycin 1 g IV
immediately and after 12h (two total doses).
For penicillin allergic: Aztreonam 2 g IV immediately and q8 hours (three total
doses); Vancomycin 1 g IV immediately and after 12h (two total doses) [21].
E. Krasin
Immunocompromised Patients
There is no conclusive evidence suggesting that HIV-positive patients experience
a higher infection rate during elective surgery or trauma, and therefore, longterm antibiotic therapy is not warranted for these individuals. Despite the
acknowledged heightened risk, there is insufcient evidence to justify deviations
from standard antibiotic therapy for diabetic patients, or those with rheumatoid
arthritis [17].
Local Antibiotics
High-quality evidence for combined local/ systemic prescription is scarce in orthopaedic surgery and particularly in surgery of the shoulder and elbow. The role of
local wound antibiotics needs to be further established in future research [7].
The interest of combinations such as cefazolin and vancomycin in preventing
periprosthetic knee infections remains uncertain, as strong prospective studies are
lacking [22]. The risk of developing acute renal failure is a major drawback of this
combination [23].
3 Controversies inAntibiotic Prophylaxis inOrthopaedic Surgery
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45
Future Developments
The task of creating a vaccine capable of preventing Staphylococcus aureus infection
has proven to be formidable. This bacterium is a commensal organism found in the
nasal mucosa and skin of humans, and it has developed a sophisticated arsenal specically designed to evade the human immune system. However, the development of an
effective vaccine holds the potential to address the escalating concerns of antibiotic
resistance and the emergence of vancomycin-resistant staphylococci. Currently, there
are at least ve vaccines against Staphylococcus aureus that are undergoing various
stages of clinical trials. Concurrently, research has also focused on bacteriophages,
monoclonal antibodies, centyrins (monoclonal antibody mimetics), and novel types of
antibiotics. Some of these approaches have shown promising results in human testing.
Additionally, various strategies have been explored in preclinical settings to enhance
the delivery of anti-staphylococcal drugs for specic infections, including skin and
soft tissue infections, implant-associated osteomyelitis, and pneumonia [24].
Conclusion
First generation cephalosporins are still popular; second-generation cephalosporins
offer greater protection against Gramnegative bacteria, but have reduced efcacy
against staphylococci. Our recent results clearly indicate a worrying increase in
resistance to clindamycin [12]. The choice of vancomycin for this task also presents
a number of challenges [25]. Thus, a single regimen will hardly be ideal for all
patients, and risk assessment should precede prophylactic prescriptions.
A shorter duration of antibiotic prophylaxis can be just as effective in preventing
SSI as a longer duration, while reducing the risk of developing antibiotic resistance.
A single dose of cefazolin administered 1h before surgery was as effective as a
three-dose regimen to prevent SSI in patients undergoing pure orthopaedic procedures, such as joint replacement [26]. In cases where there is a high prevalence of
antibiotic-resistant bacteria, the use of alternative antibiotics or combinations
thereof may be necessary to provide adequate prophylaxis.
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E. Krasin
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