Prevention of Infection
L. Frommelt
Summary
This chapter deals with precautions to prevent surgical- site infection in patients undergoing total hip arthro- plasty. The precautions are divided into three groups:
general, preoperative and precautions in the operating theatre. Measures taken in the theatre are categorised as precautions that avoid contamination of the wound and those which prevent bacterial contamination from inducing postoperative infection. Procedures to improve the host’s own defence and perioperative prophylaxis with antimicrobial agents are discussed, and recom- mendations for proper use of antibiotics with respect to choice, timing and frequency of administration are given. The different measures are categorised by level of evidence as proposed by the US Agency for Health Care Policy and Research.
Introduction
Periprosthetic infection of total hip arthroplasty (THA) is a rare complication after this frequently performed surgical procedure. It may lead to disaster for the patient.
Patients undergo total hip arthroplasty in order to get rid of pain and regain their mobility. What they get, if infec- tion occurs, is immobility, pain and a condition that may even be life-threatening.
Every operation harbours the risk of surgical infec- tion because it is impossible to completely avoid bacterial contamination in the operating theatre. The source of these infections is human bacterial flora. Whether con- tamination leads to infection depends on the number of bacteria introduced during surgery, the virulence of the bacteria and the condition of the host’s defence. If the
host’s defence is unable to balance the bacterial attack, surgical infection will result. Unfortunately, the presence of foreign material suppresses the host’s defence locally.
Thus, the total joint prosthesis is at risk of being infected even by low grade pathogens such as coagulase-negative staphylococci and propioni bacteria.
Avoiding microbial contamination and defeating peri- prosthetic infection before it becomes established is the most effective way of protecting orthopaedic devices from infection.
One of the outstanding advantages of THA is that in most cases it is an elective procedure that can be planned.
This gives the orthopaedic surgeon the opportunity for meticulous preoperative management.
Unfortunately, most precautions against periprosthet- ic infection are not based on medical evidence. They are mostly empiric, sometimes of low value and expensive.
These precautions will be discussed with respect to the pathogenesis of periprosthetic infection and com- monly accepted standards.
Pathogenesis of Periprosthetic Infection
Periprosthetic infection is a foreign-body associated in- fection. The problems result from the interaction between the foreign body and host defence and also between bacteria and the foreign body. The site of infection is primarily the interface between the bone and the foreign material.
In most cases, micro-organisms from human bacterial
flora gain access to the surface of the prosthesis during the
THA procedure. Blood-borne infections and infections
which reach the site of infection from other sources are less
frequent. Lidwell and co-workers stated that more than
90% of infections during the first year after implantation are due to bacterial contamination during surgery [22].
Bacteria, Host Defence and Foreign-Material Surfaces
To understand how periprosthetic infection starts it is necessary to understand that bacterial interaction with the foreign-material surface is a crucial factor. Specialised bacteria are able to colonise surfaces by forming a biofilm (
⊡Fig. 14.1). This biofilm protects them from the host’s defence mechanisms and these sessile bacteria are also highly resistant to antimicrobial agents [9, 18, 39]. Inside the biofilm, bacteria may spread along the surface of the implant. Periprosthetic infection begins when some of them switch back to planktonic forms and induce infec- tion in the adjacent tissue – periprosthetic osteomyelitis [16]. The period between colonisation and clinically de- tectable infection may last for months, even up to about three years.
In the presence of foreign bodies, a contamination as low as 100 colony-forming units (CFU) is sufficient to induce an infection in contrast to 10,000 CFU without foreign material [12]. This effect is due to the diminished clearing capacity of phagocytosis by leucocytes in the presence of foreign material [39].
Precautions to Prevent Periprosthetic Infection
Prophylaxis against periprosthetic infection consists of several elements: choosing a period for prosthesis implan- tation when the host’s own defence is in optimal condition, avoiding contact between the patient and germs adapted to the hospital environment, and avoiding bacterial contami- nation in the operating theatre. The second approach is to
reduce bacterial contamination in number and if possible to prevent bacteria from colonising the prosthetic device.
Quite a large number of precautionary measures are taken. Some of them have the quality of rituals and there is little or no evidence that these procedures are of any value. Some of them are useless for preventing surgical- site infection, but they are of some value in the sense that they enhance the awareness of operating theatre staff for this problem and thus induce appropriate behaviour.
The procedures are categorised and ranked in order of evidence levels. The definitions of the types of evidence are those used by the US Agency for Health Care Policy and Research [1].
Levels of evidence:
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised con- trolled trial.
IIa Evidence obtained from at least one well-designed controlled study without randomisation.
IIb Evidence obtained from at least one other type of well- designed quasi-experimental study.
III Evidence obtained from well-designed non-experi- mental descriptive studies, such as comparative stud- ies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities.
General Precautions
Most pathogens in periprosthetic infections originate from human bacterial skin flora. Therefore, the length of time patients are exposed to germs in the hospital envi- ronment should be as short as possible in order to avoid colonisation by these bacteria.
Patients undergoing THA should be separated from patients treated in general surgery. If epidemiology shows a high prevalence of multi-resistant pathogens, like meth- icillin-resistant Staphylococcus aureus (MRSA), patients should be screened for these organisms and decontami- nated preoperatively. Biant and co-workers [3] stated that these precautions lead to a significant reduction in the number of infections by MRSA in a British hospital (Cat. Ib).
The blood glucose of patients suffering from diabetes mellitus must be monitored meticulously, pre- and post- operatively. Blood–glucose levels exceeding 300 mg/dL postoperatively increase the odds for surgical-site infec- tion (SSI) from 2.54 to 3.32 compared with patients with glucose levels lower than 250 mg/dL (Cat.Ib) [3].
In patients treated with immunosuppressive drugs, the dose should be reduced to a tolerable amount. If pos- sible, immunosuppressive therapy should be discontinued
14
⊡ Fig. 14.1. Electronmicroscopy of staphylococcus with biofilm forma- tion. (Reprinted with permission from Peters G (1998) ‘Plastikinfektio- nen’ durch Staphylokokken. Dt.Ärztebl 85:C-204–C-208)
perioperatively. Bacterial infections such as urinary-tract infection, infected teeth, pyoderma or other bacterial lesions should be treated before THA is performed.
Precautions Before Operation
Shaving the Site of Operation
There is a long tradition of removing hair at the operation site in order to reduce the risk of wound infection. Cruise and Foord [10] showed that shaving may itself be a risk factor because of micro-lesions in the skin. Several studies have found no strong evidence against preoperative hair removal. However, there was strong evidence to recom- mend that when hair removal is considered necessary, it should not be removed by shaving but by a depilatory cream or electric clipping, preferably immediately before surgery (Cat. Ia).
Preoperative Showering
The patient’s skin is a major source of bacterial contamina- tion in clean operations. Traditionally, patients are asked to bathe or shower with or without disinfectant soap.
Cruise and Foord [10] found no significant reduction of the postoperative infection rate. Ayliffe [2] showed that preoperative washing with an antiseptic did not reduce the infection rate even though there was evidence that the bacterial burden of the skin was temporarily reduced.
Many other studies have also come to the conclusion that antiseptic showers do not reduce the incidence of surgi- cal-site infection (Cat. Ib).
Precautions in the Operating Theatre
Reducing Bacterial Contamination of the Wound Preoperative Hand Hygiene of the ‘Scrub’ Team. Hand decontamination is an important contribution to reduc- ing infections. Unfortunately, there is no evidence as to which method is more effective in reducing postoperative infection rates. Alcoholic disinfectants are appropriate for reducing skin bacteria. Rehork and Rüden [32] sug- gested initial hand-washing for 5 minutes followed by disinfection using an alcoholic disinfectant for 3 minutes.
If further decontamination is necessary within the next 60 minutes, no hand-washing is necessary but alcoholic hand-rubbing for 1 minute is required. If the time exceeds 60 minutes, the whole procedure has to be repeated. In the British Medical Journal editorial is was recommended that alcohol hand rubs should replace washing as the recommended method of hand hygiene [35]. However, hand decontamination before operation is recommended on the evidence level of Category IV, because it is impos- sible to design studies without the knowledge of strong theoretical rationale.
Preparation of the Patient’s Skin. For disinfection of the skin at the site of operation, aqueous iodophore prepara- tions have an excellent bactericidal effect comparable with alcohol preparations. Some preparations combine the al- cohol with iodophore or chlorhexidine.
The ideal antiseptic should be effective on a broad spec- trum of pathogens; in particular it should have a rapid and persistent effect on gram-negative and gram-positive bacteria, on fungi and also viruses. It should be resistant to inactivation on organic material like blood or discharge. It should be non-toxic and initiate no allergic reaction.
Skin antiseptics must be supplied in ready-for-use dilution in small, single-use containers. Multiple-use con- tainers can be contaminated by resistant micro-organisms which can be dispersed to the next patient. If multi-use bottles are used, they must be marked with the date of first use and the local infection control committee should give recommendations for a ‘use by date’ which is differ- ent from the manufacturer’s expiry date. These containers must not be refilled. Alcohol-based preparations must be allowed enough time to dry completely; otherwise the patient is at the risk of burns when electro-surgery is used (Cat. Ib).
Protecting the Wound. Adhesive incisional films were first used in the early 1960s. The idea was to prevent bac- teria from the patient’s own skin flora from contaminating the surgical wound. These films adhere to the complete operative field and are surrounded by linen or disposable drapes. However, there is no evidence that these incise drapes are able to reduce the incidence of post-operative wound infection. A similar approach is the use of incise films with antiseptic impregnation. These reduce re-colo- nisation of the skin, but they do not appear to reduce the incidence of surgical-site infection as well [6]. In conclu- sion, there is no benefit or evidence that incisional drapes reduce the incidence of SSI (Cat. IIb).
Textiles in the Theatre. Textiles are used for garments and drapes in the theatre. Linen is used for different pur- poses in operating departments:
▬ surgical suits which staff change into when entering the department
▬ garments worn by patients
▬ sterile gowns worn by the ‘scrub’ team
▬ sterile drapes used around the operation incision.
Surgical suits and patient’s linen have to be clean but not
sterile. Sterile coats worn by the ‘scrub’ team and drapes
are used as a barrier to prevent micro-organisms from
passing from operating theatre staff through garments to
the surgical wound, or, if the clothing becomes wet, by
capillary action called bacterial strike-through. Standard
cotton fabrics with a pore size of 80–100 µm are not suit-
able because bacteria are dispersed into the air by small
epithelial cell fragments measuring about 20 µm. To pre- vent bacterial strike-through, the textile material must be waterproof [27]. Fabrics used for surgical purposes have to prevent fluid penetration and need a pore size smaller than 20 µm whether they are woven or not. Nowadays, non-woven disposable clothing is more frequently used.
The barrier also protects staff from infections which can be acquired from patients such as hepatitis or HIV infection.
In conclusion, theatre gowns and drapes must be sterile and should be made of waterproof material with a pore size of less than 20 µm. Disposable material is preferable. Other surgical linen needs to be clean, but not sterile (Cat. Ib).
Facemasks. There is no reliable evidence that facemasks reduce postoperative infections. However, they should be used in joint replacement, where even low numbers of pathogens are able to induce foreign-body infection.
On the other hand, facemasks protect operating the- atre staff from splash infections, which can be caused by blood and discharge. Masks should be worn exclusively in the operating room and must be changed if they become damp or contaminated, and for the next operation in any case.
Facemasks should be worn in the theatre for the pro- tection of the wearer. Unfortunately, there is only insuf- ficient evidence that they also contribute to protection of the wound, but theoretical rationale makes it reasonable to wear facemasks during total joint replacement proce- dures (Cat. IIb).
Gloves. In joint replacement surgery double gloves should be worn by the ‘scrub’ team. Gloves act as a bar- rier between the wearer and the wound. They protect the wound from becoming contaminated by bacteria from the surgeon’s hands and they prevent the surgical team from viral infections. Double gloves are necessary because surgical gloves are not as fluid-proof as one might expect.
Randomised studies have shown that the leakage for water can be reduced by three to nine times if two pairs of gloves are used [11]. In conclusion: Wearing double gloves is reasonable for the ‘scrub’ team and enhances the barrier function of gloves (Cat. Ia).
Theatre Ventilation. Periprosthetic infection can be in- duced by a small number of pathogens and also by low-grade pathogens, which play only a small role in the pathogenesis of infections not associated with foreign bodies. Even though most of these infections originate directly from the patients’ own skin flora, studies suggest that some of these infections are airborne and can be pre- vented by ultra-clean air ventilation systems like vertical laminar air flow [15, 23, 30]. Laminar air-flow units in combination with body exhausts are very effective in re-
ducing airborne pathogens in number, but the number of infections caused by airborne pathogens is probably low anyway. Evidence for the reduction of the postoperative infection rate exists only for artificial joint-replacement procedures. In 1970, Charnley, who introduced ultra- clean air supply into artificial joint replacement surgery, suggested that the concept of laminar air flow should be revised. He pointed out that it is crucial to avoid con- tamination of air in the theatre by means of clothing that is impermeable and does not allow the passage of skin particles (contaminated with bacteria). Furthermore, the operation field should be separated from other parts of the theatre [7]. In conclusion, ultra-clean air units are beneficial in artificial joint replacement, but some sur- geons and bacteriologists are of the opinion that it might be possible to obtain the same effect with less technical effort. If laminar air flow is used, it must be stable against influences from the surrounding areas and the deposit for sterile surgical instruments has to be in the clean area as well. Ultra-clean units may serve Category Ib, but a retrospective study by the Norwegian Register [13] sug- gests that there is no difference between ordinary venti- lation of the operating theatre and theatres with laminar flow ventilation (Cat. III).
Improving the Host’s Own Defence
The following precautions cannot avoid bacterial con- tamination of the wound but they are able to reduce sub- sequent surgical-site infection to a certain extent and are therefore of supplementary value.
Normothermia during Operation. Patients in operating theatres are chilled by mechanical ventilation systems because they are only lightly dressed. If body temperature drops by a mean of 1.5 °C, the rate of postoperative infec- tions including surgical-site infection is higher. Patients can preferably be warmed up by warmed air in the theatre [19, 24]. The mechanism is that normothermia avoids stress, which can lead to hormonal suppression of the host’s defence. Melling and co-workers [26] reported a reduction in the incidence of infection of about 50% in clean surgery. Although this has not been investigated for total joint-replacement surgery, the principle is convinc- ing and well studied (Cat. IIb for THA).
Oxygen During Operation. Some studies suggest that providing 80% oxygen instead of 30% during the opera- tion reduces the incidence of postoperative wound infec- tion by 50% [17, 31]. These studies were performed in colorectal surgery. The mechanism behind this theory is that macrophages are activated by oxygen-dependent stimulation. O’Connor [29] mentioned liberal postopera- tive use of oxygen as a co-factor for successful and un- complicated wound healing. If this is true, this principle should work in joint replacement as well (Cat. IIa).
14
Defeating Bacteria Before Infection Becomes Established
Perioperative Antibiotic Prophylaxis
It is well known that antimicrobial agents are useful in preventing postoperative wound infection. Nevertheless, antibiotics are used not only as a therapy against already existing infections but also to prevent an infection that has a good chance of becoming established on a prosthetic device. In view of increasing bacterial resistance to anti- biotics, prophylactic use should be prudent and based on reasonable arguments. The problems involved in prophy- lactic use are which antimicrobial agents should be given, when and for how long.
Timing the Administration of Antimicrobial Agents for Prophylactic Use. The knowledge that correct timing determines the efficacy of perioperative antibiotic prophy- laxis goes back to the early sixties. Burke [5] studied the timing in animal experiments. The study was designed as follows: He set a standardised skin lesion and inoculated this lesion with living staphylococci or with dead bacteria of the same strain. In addition, he applied antibiotics ac- cording to a time schedule. The animals were exposed to only one dose of antimicrobial agents. The animals were examined at intervals of one hour before incision to six hours afterwards. He found out that the result in the animals inoculated with living bacteria was as good as in animals inoculated with dead bacteria, provided antibiot- ics were given one hour before incision. Antibiotics ad- ministered six hours after incision had no effect at all. The results in this group were equal to those of the animals inoculated with living bacteria but not given antibiotics.
Several studies were carried out in humans and showed the same results, even in placebo-controlled studies [34].
Classen and co-workers [8] showed that administration of antibiotics three hours before incision was as worthless as administration six hours after incision. Good timing is therefore an important principle in all types of surgery.
This applies to THA as well (Cat. Ia).
Duration of Antimicrobial Application for Prophylactic Use. In the past, the duration of antimicrobial prophylaxis was the subject of controversial discussion. Antibiotics were used for three days to three weeks. Nelson [28] showed that in orthopaedic surgery 7 days of antibiotics is no better than one day. Williams [36] showed that 3 days is as no better than one day. A lot of studies in other surgical specialities support these findings. In compliance with the recom- mendations of the American Academy of Orthopedic Sur- geons (AAOS), perioperative prophylactic use of antibiotics should be discontinued within 24 hours (Cat. Ia).
How Many Doses of Antibiotics? Theory suggests that supplementary doses according to the half-life of the an-
timicrobial agent used are beneficial. Unfortunately, there are no studies supporting this theory on a good evidence level. Well-designed studies are required to support the expertise of opinion leaders and advisory committees.
Until then, this practice corresponds to evidence level IV.
The concentration of prophylactic antibiotics is reduced by blood loss or transfusion of replacement serum, especially if this occurs during the first hour of surgery when the drug levels are high [33, 37]. An addi- tional dose of prophylactic agent is therefore necessary if the blood loss exceeds 1,500 mL during surgery or hae- modilution is above 15 mL/kg (Cat. II a/b).
Choice of Antimicrobial Agents in Artificial Joint Re- placement. To prevent postoperative infection after sur- gery, first- and second-generation cephalosporins, espe- cially cefazoline, are recommended as the first-line agent by most guidelines. If a patient is allergic to beta-lactam agents, vancomycin is recommended as a second-line antibiotic. Vancomycin may also be chosen when the epi- demiologic situation suggests a prevalence of pathogens resistant to cephalosporins (Cat. Ia).
The increasing prevalence of Staphylococcus aureus (MRSA) raises the issue of glycopeptide prophylaxis against MRSA and methicillin resistant Staphylococcus epidermidis (MRSE) infections in artificial joint replace- ment. However, clinical trials have failed to show that glycopeptides are superior to beta-lactam drugs in com- bating MRSE [37]. It is conceivable that beta-lactam drugs are still effective against infections by MRSE or MRSA. Widespread use of glycopetide agents harbours the additional risk of increasing the prevalence of vanco- mycin resistant enterococci (VRE) and the induction of vancomycin resistant MRSA or MRSE.
Additional Doses After the End of the Operation. Ad- ministration of additional doses of antimicrobial agents for prophylactic use has been discussed as controversially as the duration of prophylaxis. A large study of 2,651 hip replacements in the Netherlands found no difference be- tween cefuroxime prophylaxis used once or three times.
Joint infection occurred less often in the three dose group (0.45% versus 0.83%) but the difference was not statis- tically significant [38] (Cat. Ib). Another more recent retrospective study carried out by the Norwegian Register suggests that three and even four doses within 24 hours are more effective than one dose alone (
chapter 3.7). It is astonishing that this refers to all complications leading to removal of the prosthesis, whereas the differences for periprosthetic infection were only slight [13] (Cat. III).
As long as there are no prospective randomised stud-
ies available there is no high-level evidence regarding
postoperative administration of supplementary doses of
prophylactic antibiotics, and it is difficult to give proper
recommendation. The problem stays unresolved at the
moment and surgeons should be free to give supplemen- tary doses within 24 hours after surgery.
Preventing Bacteria from Colonising the Surface
The idea of incorporating antibiotics in PMMA-bone-ce- ment as a prophylactic measure against infection was in- troduced by Buchholz and led to gentamicin-impregnated bone cement [4]. In a study comparing gentamicin-loaded bone cement versus systemic antibiotic prophylaxis, the results were in favour of local application of gentamicin (Cat. IIa). Another retrospective study by the Norwegian Register suggests that the combination of local application of antibiotics and systemic antibiotics is more efficient for prophylaxis than local antibiotics in bone-cement or sys- temic administration of antimicrobial agents alone [14]
(Cat. III). The Norwegian Register studies almost exclu- sively total joint replacement fixed with bone cement. It is therefore prudent to use gentamicin-loaded bone cement in combination with systemic antibiotics for perioperative prophylaxis. There is no equivalent for cementless im- plants and there are no studies suggesting that cemented joint replacement has more favourable results with regard to surgical-site infection.
Conclusion
Prevention of foreign-body associated infections means reducing the rate of contamination, which may lead to colonisation of prosthetic devices. Whether infection oc- curs or not depends on several circumstances: the extent of bacterial contamination, the reduction of the number of pathogens contaminating the wound, and the vigilance of the host’s own defence. There are therefore three principle approaches to the prevention of periprosthetic infection:
▬ separation of the surgical wound from sources of potential contamination like theatre gowns, gloves, drapes and ventilation systems;
▬ measures to enhance the host’s own defence, like maintenance of normothermia during surgical proce- dure, high-level oxygen supply to the patient during the procedure or meticulous perioperative control of serum glucose levels;
▬ the use of antimicrobial agents for perioperative pro- phylaxis according to current guidelines.
Not all precautionary measures are supported by good levels of evidence and there are some, which can be omit- ted because there is no evidence that they are of any value.
Most of the practices contribute to the prevention of sur- gical-site infection. Success results from a cascade of small steps in the same direction. The contribution made by one
of the single steps may be not spectacular, when all steps are added together they result in a better outcome.
Most THA procedures are elective. This gives ortho- paedic surgeons the opportunity to ensure optimal pre- operative management. At the time of operation, the patient should be in a good state of health. Distant sites of infection like urinary-tract infection or pyoderma should be treated before the patient is admitted for THA. Pre- existing metabolic disorders like diabetes mellitus should be controlled as far as possible.
The preoperative stay of the patient in hospital should be as short as possible. Diagnostic or preoperative proce- dures should be performed on an outpatient basis when- ever possible.
Hazardous techniques like shaving the site of opera- tion the evening before THA should be avoided.
Operating theatre staff should take all precautionary measures to separate the surgical wound from bacte- rial contamination. Staff must be aware that that their behaviour in the theatre contributes to the reduction of postoperative wound sepsis.
Perioperative antimicrobial prophylaxis is not a sub- stitute for this behaviour, but prophylaxis with antimicro- bial agents is of supplementary benefit for the patient if handled properly.
It is impossible to avoid all surgical-site infections, but quite a large number can be avoided if the right steps are taken at the right time.
Take Home Messages
I I
▬
Periprosthetic infection in total hip arthroplasty is a rare complication after this frequently performed procedure, but when it occurs it can mean disaster for the patient. Therefore, all measures to avoid postoperative infection must be taken.▬
Precautions start at the time of patient’s first contact with the surgeon. The aim is to reduce risks that derive from the patient’s concomitant diseases and choose a period for THA when the patient is in an optimal state of health.▬
Most pathogens leading to infection originate from the human skin flora but some derive from the en- vironment adjacent to the wound. Procedures that influence the intactness of the patient’s own skin flora, like shaving the evening before operation, may be omitted. Reasonable precautions to separate the wound from bacterial contamination must be taken.▬
Precautions that reduce bacterial contaminants in number and improve the host’s own defence are beneficial. The most effective measure is periopera- tive prophylaxis using antimicrobial agents.▬
Timing, the choice of antimicrobial agent and dura- tion of administration are crucial for the success of perioperative antibiotic prophylaxis.14
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