Perioperative systemic antibiotic prophylaxis

7 Perioperative systemic antibiotic prophylaxis H. A. L. C L A S E N E R E. J. V O L L A A R D

GENERAL ASPECTS OF PROPHYLAXIS Surgical wound infection

Vital tissue will not become infected even when large numbers of pathogenic bacteria are introduced, but the presence of a foreign body, such as a suture, dramatically reduces the number of bacteria required to cause infection (Elek and Conen, 1957). A perfectly sutured surgical wound is able to resist heavy contamination, while the best aseptic technique will not prevent infection of a clean surgical wound that has been roughly sutured (Dunphy and Jackson, 1962). Preservation and restoration of the vitality of the surgical wound is therefore the most important factor in the prevention of surgical wound infection. Sutures tied too tightly will produce infected wounds (Rosenberg et al, 1975). Surgical skill may differ considerably among surgeons (Fielding et al, 1980). The individual surgeon's role in the prevention of surgical wound infection has been strongly pointed out by Cruse and Foord (1980), using prospective postoperative wound surveillance. They found that surgeons' results improved when they were compared with each other. This method is gaining acceptance as an important measure in the prevention of infection in surgery (Condon et al, 1988; Mishriki et al, 1990; Wilson et al, 1990). The maintenance or restoration of normal physiological characteristics including blood volume, oxygenation and perfusion has been shown to be the key to preventing infectious complications. Hunt's work demonstrating the role of Pao2 and tissue oxygen levels in wound healing and resistance to infection emphasizes the importance of maintaining and supporting normal physiologic characteristics (Hunt, 1987). Control of the stress response--the inevitable reaction to surgery--has been shown recently to be feasible (Meakins, 1991). Nutrition and regional anaesthesia may influence the stress response and may improve the control of infection (Dempsey et al, 1988; Kehlet, 1989). Bacteria

Surgical wound infections originate from the colonized areas of the mucous membranes and the skin. BailliOre's ClinicaI A naesthesiology-Vol. 5, No. 1, June 1991 ISBN 0-7020-1524-5

123 Copyright 9 1991, by Bailli~re Tindall All rights of reproduction in any form reserved

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The mucous membranes of the digestive tract and the vagina are colonized by anaerobic and aerobic micro-organisms. The most important aerobic bacteria are the gram-negative bacilli (Escherichia coli, Enterobacter, Klebsiella, Proteus and Pseudomonas spp) from the digestive tract, and the gram-positive cocci (Staphylococcus aureus and S. epidermidis) from the skin. Enterococcusfaecalis, an aerobic gram-positive coccus from the gut, has to be taken into account occasionally. Among the anaerobes, Bacteroides spp. are by far the most virulent. One of the factors causing this virulence is the inhibition of phagocytosis of aerobic gram-negative bacilli. Therefore, infections involving the digestive tract and vagina are not only often mixed (anaerobic plus aerobic), but also synergistic (Lea et al, 1982; Rotstein et al, 1985). In an animal model it has been shown that therapy of intra-abdominal sepsis, and therefore prophylaxis too, should be directed against both anaerobic and aerobic bacteria (Weinstein et al, 1975). Bacteria may enter the wound with the incision of a colonized organ, such as the skin, digestive tract or vagina (endogenous pathogenesis), or on skin scales with the air of the operating room (exogenous pathogenesis--see Chapter 1). The intrinsic pathogenicity and the number of bacteria are two major determinants of infection (Leonard et al, 1990; Polk and Lopes-Major, 1969). The number of species of enteric bacteria contaminating an abdominal wound was found to be directly related to the rate of infection (Pollock and Evans, 1983; Pollock et al, 1986). Epidemics of airborne infections with staphylococci and streptococci have been clearly associated with the presence of dispersers in the operating room (Ayliffe and Lowbury, 1982; Mastro et al, 1990). In joint replacement surgery, the number of bacteria in the air is directly related to the rate of infection (Lidwell et al, 1983a).

Antibiotic prophylaxis Although surgical technique is the most important determinant of the resistance to infection of the wound (Dunphy and Jackson, 1962; Rosenberg et al, 1975; Fielding et al, 1980; Edlich et al, 1988), antibiotics may be formidable aids if administered at the right time.

Experimental Howes (1946) found that antibiotics administered at the moment of heavy contamination of surgical wounds prevented infection even when some traumatized tissue was present, while the same antibiotic treatment was ineffective when given 3 hours later; the same treatment could then prevent infection only when the traumatized tissue was first removed. Howes' explanation that leucocytes protect the bacteria from being killed by phagocytosis, when unable to digest them because of the heavy loading, still seems plausible today. Miles et al (1957) and Burke (1961) showed that during the operation there is a 'decisive period' in which the resistance to infection of the wound is lowered and in which 'primary lodgment' of

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bacteria may take place. When contaminating bacteria meet a sufficient concentration of antibiotics in this period, no infection will occur. After the bacteria have been in the wound for 3 hours, antibiotics are unable to prevent an infection.

Trials The value of the concept of the decisive period has been amply demonstrated: one dose is enough (Griffiths et al, 1976; Brennan et al, 1982; Rowlands et al, 1982; Roy and Wilkins, 1984; Shatney, 1984; Gonik, 1985; Haverkorn, 1987; Stubbs et al, 1987; Hall et al, 1989b; Jensen et al, 1990), unless the operation lasts longer than 2 hours (Galandiuk et al, 1989). Short-term peroperative antibiotic prophylaxis has been the most powerful idea in the prevention of surgical sepsis since Lister's concept of antisepsis (Burke, 1983). Choice of antibiotic agent

When bacteria reach a surgical wound, they should meet adequate concentrations of an effective antibiotic. The antimicrobial choice is based on spectrum of activity, side-effects and toxicity. Moreover, two important arguments for choosing an antibiotic for surgical prophylaxis are pharmacokinetics and costs (Bergamini and Polk, 1989a). Studies of the pharmacokinetics of antibiotic surgical prophylaxis have been reviewed by Bergamini and Polk (1989b). Gram-negative bacillary and fungal overgrowth as well as selection of resistant strains are side-effects that should be taken into account when selecting an antimicrobial (Burdon et al, 1985). For example, Clostridium difficile overgrowth has been described following one intravenous dose of several cephalosporins, especially of those cephalosporins with high biliary excretion, such as cefoperazone and ceftriaxone (Ambrose et al, 1985; Privitera et al, 1991). This side-effect is a strong argument for the choice of another cephalosporin (Vollaard et al, 1990), although the half-life (8 hours) of ceftriaxone is ideal (Hell, 1989). Two intravenous doses of cefoxitin caused five Clostridium difficile infections in 37 patients, at the s~ime time protecting less against Bacteroides infections (5 in 37 patients) than metronidazole (1 in 35 patients) (Hares et al, 1981). The two antibiotics that together cover most bacterial species causing surgical infections, and which we consider to be (at the moment) by far the 'best buy' for general surgery, are metronidazole and cephazolin.

Metronidazole Bacteroides species are the most common causes of anaerobic infections following gastrointestinal and female genital tract surgery (Percival and Cumberland, 1978). Metronidazole is very effective in treatment as well as in prophylaxis of these infections (Eykyn and Phillips, 1978; Perera et al, 1980), and has been widely used for this purpose since 1974 (Baines, 1978). It has no effect on aerobic bacteria.

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Cephazolin Staphylococcus aureus and gram-negative bacilli are the most common causes of surgical wound infections when prophylaxis is given for Bacteroides infections (Leigh, 1981). Cephazolin is very active against staphylococci and gram-negative bacilli, and has a suitable half-life of about 2 hours. A disturbing discovery is that some S. aureus strains produce a [3-1actamase that is not detected by routine susceptibility tests in the laboratory, but yet may confer resistance in vivo (Kernodle et al, 1990). This explains the failures of prophylaxis with cephazolin that occurred in cardiac surgery (Kaiser et al, 1987), but suitable laboratory tests have to be developed before the significance of this finding can be fully appreciated. A well-balanced review of this problem has been given by Sabath (1989). Norfloxacin

Urinary tract catheterization after surgery should be considered to be another procedure requiring infection prophylaxis. The newer fluoroquinolone norfloxacin has been shown to be very successful in the prevention of urinary tract infections following catheterization (Vollaard et al, 1989). The mechanism is thought to be the sterilization of the urinary tract in combination with the eradication of intestinal gram-negative bacillary carriage (i.e. gut decontamination). Fluoroquinolones are well known to achieve high faecal concentrations after excretion through the gut mucosa (Cofsky et al, 1984). Staphylococcal infections of the urine may develop in some patients after a few days of catheterization; nitrofurantoin 50 mg four times a day is the appropriate therapy. Administration

Route

Intravenous injection, starting at the induction of anaesthesia, is probably the best and surest way of administering perioperative prophylaxis. Intramuscular injections, which can be given by nurses together with the premedication of anaesthesia, will result in bad timing for many antibiotics. Infiltration of an antibiotic solution into the subcutaneous and muscular tissue at the site of incision has been reported to be effective in thoracic surgery (Walker et al, 1984). Metronidazole may be given by the rectal route, because it is well absorbed rectally (Ioannides et al, 1981; McLean et al, 1983). This route is cheaper; however, because resorption is slow, the dose should be administered at least 3 hours before operation.

r/m/ng Timing of the preoperative dose has been called the single most important factor in determining the efficacy of prophylaxis (Peterson et al, 1990a).

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Administration of parenteral antibiotics before transfer of the patient to the operating room ('on call') is 'clearly anachronistic' (Kaiser, 1986a). Intravenous administration at induction of anaesthesia is preferable. Intervals for repeat doses during long operations should be correlated with the half-life of the antibiotic chosen. When cephazolin was substituted by cephapirin, which has a much shorter half-life, a significant rise in infections occurred in vascular surgery (Kaiser, 1986b). In hysterectomy, the efficacy of single-dose cephazolin prophylaxis has been found to diminish rapidly with increasing duration of surgery, approaching zero for operations lasting 200 minutes (Shapiro et al, 1982). Under cefoxitin prophylaxis, infection rates after colorectal surgery rose from 4% to 12% when operations lasted more than 215 minutes (Coppa and Eng, 1988). For cephazolin we use a 4-hour interval, with one dose postoperatively at the most. Policy

Management of the antibiotic arsenal in the hospital should be well regulated for scientific as well as for financial reasons. This requires agreements between medical staff and hospital management, and this may result in changes which are not liked by all medical specialists (Gould, 1988) nor by the pharmaceutical industry (McGowan, 1990). Restriction methods include requirement for justification, requirement for permission and automatic substitution (Ehrenkranz, 1989). Educational intervention is a non-coercive, inexpensive and well-accepted method of improvement in clinical practice; but it took 2 years of hard work before cefoxitin, used for prophylaxis in caesarean section, was replaced by cephazolin, in a highly centralized department using this method (Everitt et al, 1990). Strict regulation of antibiotic use has the advantage of better mobility in following advances in knowledge. Acceptance time for new ideas, including long-term antibiotic prophylaxis of infection in patients on mechanical ventilation (Stoutenbeek et al, 1984), seems to be about 10 years, which is too long to profit suitably from the 'explosive increase in biomedical knowledge' (Ehrenkranz, 1989). SPECIFIC PROPHYLAXIS

Colorectal surgery Reduction of the infection rate following colorectal surgery has been attempted either by preoperative reduction of the number of bacteria in the bowel or by perioperative antibiotic prophylaxis. Mechanical cleansing of the bowel without the addition of antibiotics did not reduce the number of aerobic and anaerobic bacteria in the intestinal wall, and was associated with a significantly increased risk of infection (Weidema and van den Boogaard, 1984).

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There is a general consensus that antimicrobial prophylaxis is needed in this type of surgery. From a great number of oral non-absorbable antibiotic regimens, the neomycin-erythromycin combination was the most effective one (Ehrenkranz, 1989). In colorectal surgery, bowel decontamination before operation with non-absorbable antibiotics greatly improves the effectiveness of perioperative antibiotic prophylaxis; both approaches should be therefore combined (Ehrenkranz, 1989). The newer absorbable fluoroquinolone norfloxacin has been introduced as preoperative bowel preparation in our hospital for two reasons: (a) the decontaminating properties of this drug, and (b) the poor compliance with the neomycin-erythromycin combination. Because of the exclusive aerobic cover, perioperative anaerobic cover is required (unpublished data). The quality of the mechanical bowel preparation has been found to be an important factor in the prevention of surgical infection (Morris et al, 1983a). From animal experiments it appears that 'mixed anaerobic and aerobic contamination at wound closure in colorectal surgery should be combated by prophylactic administration of antibiotics directed against both anaerobic and aerobic bacteria' (Moesgaard et al, 1986). Lincomycin and clindamycin have been used in the past. Nowadays, metronidazole is commonly used because of the severe Clostridium difficile infections caused by the interaction of lincomycin and clindamycin with the intestinal microflora (Keighley et al, 1978). Reduction of serious infections by metronidazole has been so impressive that metronidazole on its own has been considered to provide sufficient prophylaxis in colorectal surgery (Fiddian, 1978). Metronidazole provides a good anaerobic cover. Although active against anaerobes, cefoxitin (Hares et al, 1981), latamoxef (Morris et al, 1984b), and amoxycillin/clavulanic acid (Hall et al, 1989a) are less effective compared with metronidazole. However, coverage of aerobes is now advised (H6jer, 1982). In Scandinavia, doxycycline is used most often for this purpose (Midtvedt, 1988), but we prefer cephazolin because of its better antistaphylococcal action. The need to cover staphylococci in colorectal surgery has been pointed out by Morris et al (1990).

Appendicectomy A natural infection rate following appendicectomy of 30% could be reduced to 20% by either metronidazole or cephazolin, and reduced to 3% by a combination of the two drugs (Morris et al, 1980). Metronidazole was very effective in preventing infection with Bacteroides spp. (Leigh, 1978). However, one-third of patients with a perforated appendix, receiving metronidazole only, will develop surgical wound infection with aerobes (Pashby and Mee, 1978). Since a surgeon may not always be sure whether perforation has occurred or not, coverage of aerobes as well as of anaerobes has to be provided in all operations for non-perforative appendicitis (Browder et al, 1989). Another aerobe, Streptococcus milleri, needs to be covered too (Tanner et al, 1986). Mezlocillin, which is active against anaerobic and aerobic micro-organisms, has been shown to provide adequate

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prophylaxis in operations for non-perforated appendicitis (McIntosh et al, 1984). Mezlocillin may be injected into the subcutaneous tissue to be incised (Porteous et al, 1985). In gastric surgery (Morris et al, 1984b), as well as in colorectal surgery (Ambrose et al, 1983; Cann et al, 1988; Diamond et al, 1988), the poor antistaphylococcal activity of mezlocillin was evident. Gastric surgery

Although the mucous membrane of the stomach has no colonizing microflora of its own, it is contaminated continuously by the oropharyngeal microflora. In hospitalized patients the oral microflora resembles the faecal microflora, including enterobacteria and pseudomonads (Johanson et al, 1969; LeFrock et al, 1978). Infection rate following gastric surgery is high (23 %) (Sj6stedt et al, 1989). Antibiotic prophylaxis of gastric surgery should therefore cover anaerobes (Bacteroides spp.) as well as aerobes (gramnegative bacilli). Biliary surgery

A biliary tract that does not drain well frequently becomes infected by aerobic bacteria: gram-negative bacilli (Escherichia coli and Klebsiella spp.) and enterococci. Contamination of the incisional wound with infected bile is the cause of wound infection with these organisms. Since 'low risk' patients may very well have infected bile, there is no reason to withhold antibiotic prophylaxis from them (Wells et al, 1989). When the bile is sterile, incidence of wound infection is much lower and Staphylococcus aureus becomes the major cause of wound infection that should be covered by the perioperative antibiotic prophylaxis (Menzies and Ellis, 1989; Wells et al, 1989). Because of its effectiveness against enterococci, piperacillin was tried in biliary surgery, in comparison to cephazolin (Morris et al, 1983b). However, no enterococcal infections occurred in either group of 50 patients, compared with 4 in 50 controls. Cephazolin seemed somewhat more effective than cefotetan (Drumm et al, 1985). Recently, meta-analysis of the pooled results of 42 randomized controlled trials of antibiotic prophylaxis in biliary surgery led to the conclusion that there is no reason not to choose the least expensive cephalosporin (Meijer et al, 1990). Head and neck surgery

In major head and neck surgery for cancer, surgical skill is of prime importance in restoring water-tight closure of a very complex wound in a heavily colonized area of the body (Tabet and Johnson, 1990). Metaanalysis of 12 clinical trials of prophylactic antibiotics in head and neck surgery led to the suggestion that clindamycin for 1 day might be the most effective regimen (Velanovich, 1991). However, metronidazole was not used in any of these trials. Oropharyngeal decontamination by means of topical polymyxin E and

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tobramycin has been suggested as antibiotic prophylaxis in contaminated head and neck surgery (Jones et al, 1989). The abolition of oropharyngeal carriage of gram-negative bacilli and S. aureus was very successful using this regimen (van Saene and Mostafa, 1991). This oral decontamination programme should be started a few (3?) days preoperatively, and should be combined peroperatively with a parenteral antimicrobial agent covering anaerobes.

Gynaecological surgery Hysterectomy During hysterectomy, vaginal and pelvic wounds will be contaminated by the anaerobic and aerobic flora of the vagina. Local disinfection cannot eliminate this flora completely, as is clear from the high rate of infection following hysterectomy in former days. The vaginal approach is more often followed by infection than the abdominal approach, probably as a result of the more substantial tissue destruction and necrosis (Wijma et al, 1987). The reduction by metronidazole of infections following hysterectomy has been called dramatic (Seligman, 1978). Tinidazole (a nitroimidazole similar to metronidazole) reduced the incidence of clinically relevant morbidity from 44% in a control group to 10% in a treated group (Janssens et al, 1982). However, cephalosporins given with the intention of covering the aerobic vaginal flora have proved to be equally effective in preventing infections following hysterectomy (Polk et al, 1980). This has led to interesting discussions about the relative importance of aerobic and anaerobic microorganisms (Brown, 1987), but may be better explained by an effect of cephalosporins on anaerobes. Cephradine, a cephalosporin with good antistaphylococcal activity, has even been considered for antianaerobic therapy (Brumfitt et al, 1982). Cephazolin would cover not only E. coli, whichis reported to be the aerobic bacterium most frequently involved in gynaecological surgery, but also S. aureus, which is an important cause of infection of the abdominal wall wound after abdominal hysterectomy (Brown, 1987). Amoxycillin/clavulanic acid, which is active against anaerobes and aerobes, performs as well in gynaecological surgery as the combination of metronidazole and cefuroxime (Friese et al, 1989); however, the combination of cephazolin with metronidazole is to be preferred because of the cost and the major impact of amoxycillin/ clavulanic acid on the intestinal microflora. Caesarean section Wound infection. A multicentre study has shown that obesity of the patient, surgical skill and type of incision are major risk factors for wound infection after caesarean section (Moir-Bussy et al, 1984). The micro-organisms isolated most frequently from the wounds in this study were S. aureus. S. epidermidis, gram-negative bacilli (E. coli, Proteus spp., etc.), enterococci and anaerobes. An analysis of 58 controlled trials showed that routine antibiotic prophy-

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laxis in caesarean section was cost-effective (Mugford et al, 1989). Low-risk caesarean section was followed by infection in 3.7% of women who did not receive antibiotic prophylaxis and in 0.9% of women who did, and from this it was calculated that one or even three doses of cephazolin per caesarean section could save the USA $9 million a year (Ehrenkranz et al, 1990). Administration of the prophylaxis immediately after clamping the umbilical cord restricts the antibiotic to the mother and is still effective (Galask, 1987). Cephazolin has been reported to be as effective as cephamandole, while costing half as much (Peterson et al, 1990b). E n d o m e t r i t i s . Metronidazole as sole prophylactic agent has been reported to

reduce wound infections from 18% to 3.7%, and endomyometritis from 30% to 13.2% (Gerstner, 1982). Prostatic surgery

Infections following transurethral resection of the prostate are caused by the aerobic bowel flora (gram-negative bacilli and enterococci) that also causes the urinary tract infections which often already exist in candidates for this operation, especially when they carry a catheter. Selecting only infected patients for antibiotic prophylaxis is impractical because culture reports will not usually be available in time (Williams, 1981; Taylor and Lindsay, 1989), and urinary bacterial counts of less than 105/ml tend to be neglected by the laboratory (Grabe, 1989). Extending prophylaxis from a single dose of cefotaxime to four doses over 48 hours reduced postoperative complications from 47 in 106 patients to 21 in 97 patients, probably because an urinary catheter was normally placed in the wound for 48 hours (Hargreave et al, 1984). The need to cover enterococci has been stressed (Hoogkamp-Korstanje et al, 1985; Charton et al, 1987; Taylor et al, 1988). Theoretically the fluoroquinolones including norfloxacin are promising antimicrobials in prostatic surgery because of the good penetration of these molecules in the prostatic tissues (Sabbaj et al, 1986). A possible regimen might be oral norfloxacin started 3 days before the operation, in order to obtain high prostate, bladder and gut concentrations (to prevent emergence of resistance) on the day of surgery, and possibly continued until the catheter is removed. Neurosurgery

The advisability of antibiotic prophylaxis in neurosurgery is without doubt (Haines, 1989; Savitz and Haines, 1989) especially in epidemics (Shapiro et al, 1986). The choice of antibiotic is between cephazolin and vancomycin, depending on the sensitivity of the locally prevalent strains of S t a p h y l o c o c c u s aureus (Dempsey, 1989; Savitz and Malls, 1989). Penicillin has been effective also, which suggests that wounds were colonized by low numbers of penicillinase-producing S. aureus (Cartmill et al, 1989). However, penicillin is to be avoided in craniotomy because of the risk of seizures (Michenfelder

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et al, 1990). The cerebrospinal fluid shunt infections, which may become manifest much later than the surgical wound infections, are probably caused by intraluminal contamination with S. epidermidis, and very low infection rates have been reported following irrigation with and soaking of the shunt in a gentamicin solution (Price, 1984). Vascular surgery

Staphylococcus aureus and S. epidermidis cause most infections in vascular surgery, and prophylaxis with cephazolin is advised (Conte, 1989). Cardiac surgery

Prosthetic valve endocarditis and sternal wound infection are mainly caused by staphylococci (Wilson, 1988). Skin scales carrying staphylococci may enter the cardiac and sternal wounds directly, but also indirectly with contaminated blood and air sucked into the circulation (van Oeveren et al, 1986). Therefore, an ultraclean air ventilation system, and a suction device that does not aspirate air, may be expected to lower the incidence of infection in cardiac surgery. Antibiotic prophylaxis is generally aimed at Staphylococcus aureus and S. epidermidis. In the USA, cephazolin for 2 days has been recommended, but a single-dose regimen may be as effective (Conte, 1989). Cephazolin and cephamandole, given for 3 days, may increase the numbers of methicillinresistant staphylococci colonizing the skin of cardiac surgery patients (Kernodle et al, 1988). This might be another argument for using a single dose for prophylaxis in uncomplicated cardiac cases. However, the risk of endocarditis continues after the operation because of invasive lines. When the bacterial load is low, as it should be in cardiac surgery, cephazolin will probably be effective in eradicating the methicillin-resistant staphylococci that naturally may occur as one cell in a population of 104 to l0 s (Hackbarth and Chambers, 1989). Cephazolin was clearly inferior to cephamandole in one trial (Kaiser et al, 1987), but equal to cephamandole or cefuroxime in another (Gentry et al, 1988). We think that in reporting trials, ventilation systems should be specified, in order that bacterial load may be related to the efficacy of a particular antibiotic. Teicoplanin, a promising candidate because of its antistaphylococcal activity, did not prevent sternal wound infection as well as the regular British regimen of flucloxacillin plus tobramycin (Wilson et al, 1988a). This may be explained by the low penetration of teicoplanin in subcutaneous fat (Wilson et al, 1988b). Higher doses are now tried (Wilson et al, 1989). Orthopaedic surgery

In the largest study of infections in orthopaedic surgery yet made, it could be shown that installation of the most expensive (and best) ventilation system is cost-effective (Lidwell, 1988a,b). This ultraclean air system 'should be available in any hospital undertaking the more demanding procedures of

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modern surgery' (Selwyn, 1986), such as prosthetic orthopaedic and cardiovascular surgery, and cerebrospinal fluid shunt insertions (Seal and Clark, 1986). To this list should be added revision surgery in which three times more infections occur than in the primary placement of the prosthesis (Taylor et al, 1990). Antibiotics could substitute for ultraclean air to some extent and helped to lower the infection rate when used in addition (Lidwell, 1988a). Antibiotic prophylaxis should aim primarily at Staphylococcus aureus and S. epidermidis, but coverage of gram-negative bacilli is needed too (Lidwell et al, 1983b). Although cephazolin still seems a good choice (Conte, 1989), cefuroxime might become a better one because of superior activity on S. epidermidis (Sanderson, 1989). Cephazolin and cefuroxime have been shown to reach sufficiently high tissue concentrations in joint replacement surgery (Cunha et al, 1977; Leigh et al, 1982; Leigh, 1989). In knee arthroplasty, the thigh tourniquet should not be inflated less than 10 minutes after intravenous injection of cefuroxime (Johnson, 1987). Injection into a foot vein after inflation of the tourniquet results in much higher concentrations in the tissues of the knee (Hoddinott et al, 1990). Since late infections in implantation surgery may not only be caused by micro-organisms introduced into the wound at the operation, but also by blood-borne contamination from an infectious process elsewhere in the body, patients should receive antibiotic prophylaxis for all procedures known to cause bacteraemia, and receive prompt antibiotic therapy for all infections of the skin, urinary tract and respiratory tract (Sanderson, 1989; Bell et al, 1990). For the same reason, all patients requiring urinary catheters postoperatively should receive antibiotic prophylaxis for urinary tract infection (Vollaard et al, 1989). Herniorrhaphy and breast surgery

One preoperative dose of a cephalosporin (cefonicid) reduced infections after herniorrhaphy from 4.2% to 2.3%, and from 12.2% to 6.6% after breast surgery (Platt et al, 1990). Cephazolin may be expected to be equally useful for these operations. SUMMARY

The lower the infection rate in a particular operation, the larger the trial must be to show a benefit of antibiotic prophylaxis. Recently herniorrhaphy, which is considered to be a clean operation, was shown to profit from antibiotic prophylaxis. Perioperative prophylaxis is therefore expected to be used much more widely in the future. The combination of cephazolin and metronidazole is recommended for perioperative prophylaxis because it covers the majority of surgical infections and it is cheap. Preoperative norfloxacin is promising in antibiotic bowel preparation and in the prevention of urinary tract infection following catheterization. Recommended regimens are summarized in Table 1.

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H. A. L. CLASENER AND E. J. VOLLAARD Table 1. Recommendations for perioperative antibiotic prophylaxis.

Indication

Drug

Dose

Start

All operations Oropharyngeal, gastrointestinal and vaginal Antibiotic bowel preparation Urinary catheter

Cephazolin Metronidazole

1 g IV i g IV

At induction At induction

Norfloxacin

400 mg orally

Norfloxacin

400 mg orally

5 days before operation With start of catheterization

Interval 4h 8h 12 h 12 h

Acknowledgements

The authors are grateful to Mr A. Wilkins and Mr E. van Haaren for providing the literature, and to Ms Efly Koks for typewriting the manuscript.

REFERENCES

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