7.

Wound infection
DAVID J. LEAPER

Physiology and manifestation Background. It is clear that the Egyptians knew about infection. They certainly were able to prevent putrefaction which is testified in their skills of mummification. Their medical papyruses also describe the use of salves and antiseptics to prevent wound infections. This had also been known, although less well documented, by the Assyrians and the Greeks, particularly in Hippocratic teachings, which had refined the use of antimicrobial practice. The use of wine and vinegar to irrigate open infected wounds before successful secondary closure was practised widely. Common to all these cultures, and the later Roman practitioners, was a dictum that whenever pus developed in an infected wound it needed to be drained. Galen recognised that localisation of infection (suppuration) in wounds inflicted in the gladiatorial arena often heralded recovery, particularly after drainage of the pus (pus bonum et Iaudabile). Sadly, this dictum was misinterpreted by many until well into the Renaissance; many practitioners actually promoted suppuration in wounds by application of many noxious substances, including faeces, in the misbelief that healing could not occur without pus formation. There was occasional light in this long, dark tunnel: Theodoric of Cervia, Ambroise Pare and Guy de Chauliac all realised that clean wounds, closed primarily, could heal without infection or suppuration. The understanding of the causes of infection came in the nineteenth century~ Microbes had been seen under the microscope, but Koch laid down the first definition of infective disease (Kochs postulates). These were basically that a particular microbe could be considered responsible for an infection when it was found in adequate numbers in a septic focus, could be cultured in pure form from specimens taken from the focus and could cause similar lesions when injected into another host. The Austrian obstetrician, Ignac Semmelwe is, showed that maternal mortality caused by puerperal sepsis could be reduced from over 10 per cent to under 2 per cent by the simple act of hand washing between postmortem examinations and the delivery suite. Louis Pasteur recognised that microorganisms spoilt wine and Joseph Lister applied this knowledge to the reduction of organisms in compound fractures allowing surgery without infection. However, his toxic phenol spray and principles of antiseptic surgery soon gave way to aseptic surgery at the turn of the century a technique still employed in modern operating theatres. The concept of a magic bullet which could kill microbes but not their host led to early sulphonamide chemotherapy. The antibiotic penicillin, the discovery of which is ascribed to Alexander Fleming, was isolated by Florey and Chain. The first patient to receive penicillin was Police Constable Alexander, who had a severe staphylococcal illness. He made a partial recovery before the penicillin ran out but later relapsed and died. Since then there has been a huge increase in antibiotic groups with improved antibacterial spectra. Few staphylococci are now sensitive to penicillin but streptococcal illnesses respond, although they are seen increasingly rarely in surgical practice. Many bacteria develop resistance through the acquisition of beta-lactamases which can break up the 3-lactam ring, common in the formula of many antibiotics. In general surgery, the synergy of aerobic Gram-negative bacilli with anaerobic Bacteroides spp. presents the most challenging infection. Wide-spectrum antibiotics can be given empirically to treat such

infections, or more specific, narrow-range antibiotics given based on culture and sensitivity. The range of surgery now practised owes much to rational antibiotic use faecal peritonitis may not be considered to be lethal, and wounds made in the presence of such contamination can heal primarily without infection in 8090 per cent of patients. Patients undergoing prosthetic surgery or who are immunosuppressed can be spared infection in their wounds by the appropriate use of prophylactic antibiotics. Physiology Bacteria are normally prevented from causing infection in tissues by intact epithelial surfaces, but these are broken down by surgery. In addition to this mechanical barrier, there are other protective mechanisms, i.e. chemical (such as the low gastric pH), humoral (antibodies, complement and opsonins) and cellular (phagocytic cells, macrophages, polymorphonuclear cells and killer lymphocytes). Host response is weakened by malnutrition which may present as obesity as well as recent rapid weight loss (Table 7.1) Metabolic diseases, diabetes mellitus, uraemia and jaundice may weaken defences, and disseminated cancer may also be included together with immunosuppression caused by radiotherapy, chemotherapy, steroids and acquired immunodeficiency syndrome (AIDS) (Fig 7.1 and Fig 7.2). When enteral feeding is suspended in the perioperative period, the gut rapidly becomes colonised and bacteria, particularly Gram-negative bacilli, translocate to mesentericnodes. Release of endotoxin may follow, which further increases susceptibility to infection. In these circumstances, nonpathogens become important (opportunism). The pathogenicity and size of bacterial inoculum also relates to the chance of developing an established wound infection after surgery. Poor surgical technique that leaves devitalised tissue, excessive dead space or haematoma may increase this risk. Foreign materials of any kind, including sutures and drains, promote infection. A logarithm reduction in the number of organisms is needed to cause a wound infection in the presence of a silk suture. These factors need consideration in prosthetic orthopaedic and vascular surgery. In the first 4 hours after a breach in an epithelial surface and underlying connective tissues made during surgery or trauma, there is a delay before host defences can become mobilised through acute inflammatory, humoral and cellular processes. This period is called the decisive period and it is during these first 4 hours after incision that bacterial colonisation and established infection can begin. It is logical that prophylactic antibiotics will be most effective during this time. Local and systemic manifestation Infection of a wound can be defined as the invasion of organisms through tissues following a breakdown of local and systemic host defences. Sepsis is the systemic manifestation of a documented infection, the signs and symptoms of which may also be caused by multiple trauma, burns or pancreatitis. Bacteraemia should not be confused with this systemic inflammatory response syndrome (SIRS) although the two may coexist (see Table 7.2). Septic manifestations are mediated by release of cytokines [such as interleukins (IL) and tumour necrosis factor (TNF)] and other modules from polymorphonuclear and phagocytic cells and, in its most severe form, presents as multiple system organ failure (MSOF). Infection may cause SIRS through the release of lipopolysaccharide endotoxin from the walls of dying Gram-negative bacilli (mainly Escherichia coli) and other toxins, which in turn causes release of cytokines (Fig. 7.3). A reduced defence to wound infection follows. Pathogens resist host defences by release of toxins, particularly in unfavourable anaerobic conditions, which favours their spread in wound infections. Clostridium

perfringens, which is responsible for gas gangrene, releases many spreading proteases such as hyaluronidase, lecithinase and haemolysin. Many resistant pathogens can produce beta-lactamases which destroy the beta lactam ring of antibiotics. This resistance can be acquired and passed on through plasmids. The human body harbours approximately 1014organisms. They are released into tissues by surgery, contamination being most severe when a hollow viscus is opened (e.g. colorectal surgery). Any infection which follows may be termed primary, community acquired or endogenous. Exogenous infections are usually hospital acquired (nosocomial) and are secondary, being introduced into the tissues after surgery not during it, unless introduced via inadequately filtered air in the operating theatre. A major wound infection is defined as a wound which discharges pus and may need a secondary procedure to be sure of adequate drainage (Fig. 7.4). There may be systemic signs of tachycardia pyrexia and a raised white count (SIRS). The patient may be delayed in returning home beyond the planned day. Minor wound infections may discharge pus or infected serous fluid but should not be associated with excessive discomfort, systemic signs or delay in return home (Fig. 7.5).The differentiation of major and minor wound infection is important in audit trials of antibiotic prophylaxis and is of relevance to league tables of hospital infection as major wound infections must be accounted for. Types of infection Wound abscess A wound abscess presents all the Celsian clinical features of acute inflammation: calor(heat), rubor (redness), dolor (pain)and tumour(swelling),to which can be added functio leasa (loss of function ) .it hurts the infected part is not used). Pyogenic organisms, predominantly Staphylococcus aureus, cause tissue necrosis and suppuration. Pus is also composed of dead and dying white blood cells which release damaging cytokines, oxygen-free radicals and other molecules. An abscess is surrounded by an acute inflammatory response, and a pyogenic membrane composed of fibrinous exudate and oedema, and the cells of acute inflammation. Granulation tissue (macrophages, angiogenesis and fibrobbasts) forms later around the suppuration and beads to collagen deposition. If excessive or partly sterilised by antibiotics (antibioma), a chronic abscess may result. Abscesses usually track along planes of least resistance and point towards the skin. Wound abscesses may spontaneously discharge through a surgical incision but most take 79 days to form after surgery. Many infections may present after the patient has left hospital. Abscesses may need dbridement and curettage with an exploration to break down all loculi before resolution can occur. Persistent chronic abscesses may lead to sinus or fistula formation. In a chronic abscess, lymphocytes and plasma cells are seen with sequestration and later calcification. Certain organisms are related to chronicity, sinus and fistuba formation, e.g. mycobacteria and actinomyces, and should not be forgotten. Perianastomotic abscesses may be the cause or result of anastomotic leakage. Deep cavity abscess (pleura or peritoneum) may be difficult to diagnose or locate even when there is strong clinical suspicion (Fig. 7.6). Plain or contrast radiographs may not be helpful, whereas ubtrasonography,computerised tomography, magnetic resonance imaging and isotope scans are usually accurate and may allow guided aspiration without the need for surgical intervention. The role of antibiotics in the treatment of wound abscesses is controversial unless there are signs of spreading infection (ceblulitis or lymphangitis). Surgical decompression

and curettage must be adequate and may allow resuture without antibiotics but this is also controversial. Delayed primary or secondary suture is safer. Cellulitis and lymphangitis This is the nonsuppurative invasive infection of tissues. In addition to the cardinal signs of inflammation, there is poor bocabisation. Spreading infection is typical of organisms such as f3-haemolytic streptococci (Fig. 7.7), staphylococci (Fig. 7.8) and C. perfringens. Tissue destruction and ulceration may follow, caused by release of streptokinase, hyaburonidase and other proteases. Systemic signs (toxaemia) are common: SIRS, chills, fever and rigors. These follow release of exotoxins and cytokines but blood cultures are often negative. Lymphangitis is caused by similar processes but presents as painful red streaks in affected lymphatics. Cellulitis is usually located at the point of injury and subsequent tissue infection. Lymphangitis is often accompanied by painful lymph node groups in the rebated drainage area. Bacteraemia and septicaemia These are unusual in superficial wound infections but common after anastomotic breakdown. They are usually transient and follow procedures undertaken through infected tissues (particularly instrumentation in infected bile or urine).Bacteraemia is important when prosthetics have been implanted, particularly cardiac valves. Septicaemia commonly relates to colonisation and translocation in the gastrointestinal tract and may follow anastomotic breakdown accompanied by MSOF (Fig. 7.3). Aerobic Gram-negative bacilli are mainly responsible but S. aureus and fungi may be involved, particularly after the use of broad-spectrum antibiotics. Specific wound infections Gas gangrene is caused by C. perfringens. The Gram-positive, spore-bearing bacilli are widely found in nature, particularly soil and faeces, which is relevant to military and traumatic surgery, and colorectab operations. Patients who are immunocompromised, diabetic or have malignant disease are at risk, particularly when anaerobic wound conditions are present with necrotic or foreign material. Wound infections are associated with severe local wound pain and crepitus (gas in the tissues which may also be noted on plain radiographs). The wound presents a thin, brown, sweet-smelling exudate, from which bacteria can be recognised on Gram staining. Oedema and spreading gangrene follow the release of collagenase, hyaburonidase, other proteases and a-toxin. Systemic complications with circulatory collapse and MSOF supersede without appropriate intervention. Prophylaxis in patients at risk should always be considered, particularly amputation for peripheral vascular disease. Once established, barge doses of intravenous penicillin and aggressive dbridement of affected tissues are required. The use of hyperbaric oxygen is controversial. Synergistic spreading gangrene (necrotising fasciitis) is not caused by cbostridia. A mixed pattern of organisms is responsible cobiforms, staphylococci, Bacteroidesspp., anaerobic streptococci and pepto-streptococci have been implicated. Synonyms have been associated with abdominal wall infections (Meleneys synergistic hospital gangrene) and scrotal infection (Fourniers gangrene, Fig. 7.9). Patients are almost always immunocompromised (such as diabetes mebbitus). The initial wound may have been minor, but severely contaminated wounds are more likely to be the cause. Severe wound pain, signs of spreading inflammation with crepitus and smell lead on to widespread gangrene. The extent of subdermal spread of gangrene is always much more extensive than at first is apparent. Wide-spectrum antibiotic therapy must be

combined with aggressive circulatory support and wide excision and laying open of affected tissue. Dbridement may need to be extensive. Patients who survive need barge areas of skin grafting. Treatment Following the trend to discharge patients earlier, many wound infections may be missed by surgeons unless they undertake a prolonged and carefully audited follow-up with family doctors. Suppurative wound infections take 710 days to develop, whereas cellulitis around wounds caused by invasive organisms (such as the beta-haemolytic streptococcus) appears in 3-4 days. Major wound infections with systemic signs (Fig. 7.10) or evidence of cebbubitis justify the use of appropriate antibiotics. The choice may be empirical or based on culture and sensitivities of isolates harvested at surgery. Although the identification of organisms in wound infections is necessary for audit and wound surveillance purposes, it is usually 23 days before sensitivities are known (Fig 7.11 and Fig 7.12). It is illogical to withhold antibiotics but if clinical response is poor by the time sensitivities are known then antibiotics can be changed. This is unusual if the empirical choice of antibiotics is sensible change of antibiotics promotes resistance and risks complications, such as Clostridium difficile enteritis. When the wound is under tension or there is clear evidence of suppuration removal of sutures aids evacuation of pus. There is no evidence that subcuticular continuous skin closure enhances or worsens the effect of suppuration. In severely contaminated wounds, e.g. laparotomy for faecal peritonitis, or incisions made for drainage of an abscess, it is logical to leave the skin layer open. Delayed primary or secondary suture is undertaken when the wound is clean and granulating (Fig 7.13 and Fig 7.14). Leaving wounds open after dirty operations is not practised as widely in the UK as in the USA or mainland Europe. When taking pus from infected wounds, specimens should be sent fresh for microbiological culture. Swabs should be placed in transport medium but as barge a volume of pus as possible is likely to yield more accurate results. Communication with microbiologists is essential for the most meaningful results. If bacteraemia is suspected, repeat specimens may be needed to exclude negative results. Reports on infective material can be based rapidly on an immediate Gram stain. Aerobic and anaerobic culture on conventional media allows sensitivities to be assessed by disc diffusion. The measurements of minimum inhibitory antibiotic concentrations (M1C9O in mg/litre), together with measurements of endotoxin and cytokine bevels, are usually only used in research. Many dressings are now available for use in wound care. These are listed in Table 7.3. Polymeric films are used as incise drapes and also to cover sutured wounds but are not indicated for use in wound infections. Agents that can be used to help dbride open infected wounds, others to absorb excessive exudate or to encourage epitheliabisation and formation of granulation tissue are also listed (Fig. 7.15). Prophylaxis Prophylactic antibiotics. If antibiotics are given empirically they must exert their action when local wound defences are at their beast (the decisive period). Ideally, maximal blood and tissue levels should be achieved at incision before contamination occurs. Intravenous administration at induction of anaesthesia is optimal. In long or prosthetic operations, or unexpected contamination, antibiotics may be repeated 8 and 16 hours later. The empiric choice of an antibiotic depends on the expected spectrum of organisms likely to be encountered, the cost and local policies, which are based on experience of local resistance trends. The use of the newer, wide-spectrum antibiotics

for prophylaxis should be avoided. Table 7.4 gives some examples of prophylaxis which can be used in elective surgical operations. Lower limb amputation should be covered against C. per fringens using 1.2 g of benzyl penicillin intravenously at induction or anaesthesia and 6-hourly thereafter for 48 hours. Patients with known vabvubar disease of the heart (or with any implanted vascular or orthopaedic prosthesis) ought to have prophylaxis during dental, urobogical or open viscus surgery. Single doses of wide-spectrum penicillin, e.g. amoxyciblin, orally or intravenously administered, are sufficient for dental surgery. In urobogical instrumentation a second generation of cephabosporin, such as cefuroxime, is sufficient but, in open viscus surgery, addition of metronidazole should be considered. Preoperative preparation. Short preoperative hospital stay bowers the risk of acquisition of methicibbin-resistant S. aureus(MRSA) and multiply resistant, coagulase-negative staphylococci (MRCNS). The value of personal hygiene is obvious (both patient and surgeon). Open, infected skin lesions should preclude admission to the operating theatres. The value of antiseptic bathing (usually chborhexidine) is popular in Europe but there is no hard evidence for its efficacy in reducing wound infections. Preoperative shaving should be avoided except for aesthetic reasons or to prevent adherence of dressings. Shaving should be undertaken immediately before surgery but poses a higher infection rate (over 5 per cent) when performed the night before because minor skin injury enhances superficial bacterial colonisation. Cream depilation is messy but clipping is best, with beast infection (reportedly under 2 per cent in clean wounds). Scrubbing of operators hands with aqueous antiseptics should be confined to nails for the first operation of the day (repeated extensive scrubbing releases more organisms), with washing to the elbows, repeated alone for subsequent operations. Skin preparation of the operative site is adequate with one application of an alcoholic antiseptic (over 95 per cent reduction in flora and fauna). Antiseptics in common use are listed in Table 7.5. Theatre technique and disciplines also contribute. Only careful surveillance can ensure the quality of theatre ventilation, instrument steribisation and aseptic technique. Operator skill in gentle manipulation and dissection of tissues is much more difficult to measure but avoidance of dead space, excessive use of diathermy and haematomas surely contribute. There is no evidence that drains, incise drapes or wound guards help to reduce wound infection. Similar wound surveillance is needed in postoperative care. Secondary (exogenous) nosocomial infections are related to poor hospital wound care. Outbreaks of MRSA are rare but serious. This organism also acts as a marker of adequacy of postoperative wound care but can be very difficult and expensive to eradicate. Careful audit should bead to changes in practice and follow-up should ensure that ioops are closed. It is critical that surgeons manage their own audit league tables kept by nonmedicab or related personnel must be accurate but are to be deprecated. Scoring systems are useful in audit but, in general, have only been used in wound infection research. Classification of wounds Potential for infection The best measure of wound contamination at the end of an operation, and the risk of developing infection, is to sample tissue in the wound edge. Bacteria will already be affected if antibiotic prophylaxis has been given, but the theoretical degree of contamination relates well to infection rates (Table 7.6). When wounds are heavily

contaminated or an incision is made into an abscess, continuing prophylaxis as therapy is justified. Infection rates after nonprosthetic clean surgery may be higher if looked for. Antibiotic prophylaxis is controversial. Bacteria involved in wound infection Streptococci form chains and are Gram positive on staining (Fig. 7.16). The most important is the 13-haemobytic streptococcus which resides in the pharynx of 510 per cent of the population. It is in group A of the Lancefiebd AG carbohydrate antigens. The alternative name of Streptococcus pyogenes is deserved because of its tendency to spread (cellubitis) and to cause tissue destruction through release of stretoptolysin, streptokinase and streptodornase. Strepococcus faecalis is the enterococcus in Lancefield group D (often found in synergy with other organisms) and the y-haemolytic (no haemobysis on blood agar) peptostreptococcus is an anaerobe. Both may be involved in wound infection after large bowel surgery. The ct-haemolytic Streptococcus viridans is not related to wound infections. The streptococci are still sensitive to penicillin; erythromycin and cephabosporins are alternatives in case of allergy. Staphylococci form clumps and are Gram positive (Fig. 7.17). Staphylococcus aureus is the most important pathogen in this group and resides in the nasopharynx of up to 15 per cent of the population. It can cause exogenous suppuration in wounds (and implanted prosthetics), and MRSA can be involved in epidemics. Doctors and nurses may need to be swabbed and carriers identified and treated in an epidemic. Infections are usually localised (see Wound abscess above). Most hospital S. aureus strains are now f3-lactamase producers and are resistant to penicillin. Sensitivity to flucloxacillin, vancomycin, aminoglycosides, some cephabosporins and fusidic acid (used in osteomyelitis) is still high. Staphylococcus epidermidis (syn. albus and most conventionally coagulase-negative Staphylococcus) was regarded as a commensal but is now recognised as a major threat in prosthetic (vascular and orthopaedic) surgery. It exists in hospitals as a nosocomially acquired organism MRCNS and is resistant to many antibiotics. Clostridial organisms are Gram-positive, obligate anaerobes which produce resistant spores (Fig. 7.18). Clostridium perfringens is the cause of gas gangrene (Specific wound infections above). Clostridium tetani causes tetanus following implantation in the tissues or a wound by release of the exotoxin tetanospasmin. A short prodromal period is related to development of severe spasms including opsithotonus, respiratory arrest and death. A longer prodromal period of 45 weeks is associated with a much milder form of the disease. Prophybaxis with toxoid is the best preventative treatment but, once established, minor dbridement with benzyl penicillin and rebaxants (even with ventilation) may be required. The use of antitoxin is controversial. Clostridium difficile is the cause of pseudomembranous colitis but is not involved in wound infection. Aerobic Gram-negative bacilli (AGNB) are normal inhabitants of large bowel. Escherichia coli and Klebsiella spp. are lactose fermenting; Proteus is nonlactose fermenting. Most organisms in this group act in synergy with Bacteroidesto cause wound infections after bowel operations (in particular appendicitis, diverticubitis and peritonitis). The pseudomonads tend to cobonise burns and tracheostomy wounds, as well as the urinary tract (all members of this group are a cause of urinary tract infection). Pseudomonads may be regarded as markers and cobonise wards and intensive care units from which they may be difficult to eradicate. Surveillance of cross-infection is important in outbreaks. Hospital strains become resistant to 3lactamase which can be transferred by pbasmids and individual sensitivity testing may

be needed. Wound infections only need antibiotic therapy when there is progressive or spreading infection with systemic signs. The aminogbycosides are effective but some cephalosporins and penicillin may not be. Many of the new quinolones, e.g. ciprofloxacin, or carbapenems, e.g. meropenem, are useful in severe infections. Bacteroides are nonspore-bearing, strict anaerobes which cobonise the large bowel, vagina and oropharynx. Bacteroides fragilis is the principal organism which acts in synergy with AGNB to cause wound infection after colorectab or gynaecological surgery. They are sensitive to the imidazobes, e.g. metronidazole, and some cephalosporins, e.g. cefotaxime. Principles of antimicrobial treatment Antimicrobials may be used to prevent (Prophylaxis above) or treat established wound infection. The use of antibiotics for established infection in wounds ideally requires the isolation of the bacterium and a determination of its sensitivity; this is the overriding first requirement, for after antibiotics are administered, the clinical picture may be confused, the patient no better, and the opportunity to make a precise diagnosis has been lost. However, it is unusual to have to treat wound infections with antibiotics. Only spreading infection or signs of systemic sepsis really justify them. Appropriate treatment must include drainage of pus and dbridement if necessary.Presented with pus, or other material draining from a wound, the microbiologist can isolate the causative organisms and this may guide therapy. There are two approaches to treatment: the use of a narrow-spectrum antibiotic to treat a known sensitive infection, e.g. an MRSA sensitive to flucloxacibbin (or if not, vancomycin), isolated from pus; the use of broad-spectrum antibiotic combinations where the organism is not known or where it is suspected that there may be one, two or more, usually gut-derived bacteria responsible for the infection acting in synergy. Thus, during and following emergency surgery within the abdomen, or requiring the opening of bowel where any of the gut organisms may be responsible for subsequent peritoneal or bacteraemic infection, a combination of broad-spectrum penicillin, such as ampicillin or mezbociblin with an aminoglycoside, e.g. gentamicin, and metronidazole may be used postoperatively to support the patients own body defences. Alternatives are a cephalosporin, e.g. cefuroxime, with metronidazole (increasingly popular as gentamicin toxicity and monitoring of bevels are avoided), or monotherapy using a carbapenem or quinolone. In surgical units with multiple resistant Pseudomonas or other Gram-negative species (such as Klebsiella) which have become resident opportunists, there may become a need for a rotation of antipseudornonal and anti-Gram-negative chemotherapy between the broad-spectrum penicibbins, e.g. azbocilbin 2 g i.v. 8-hourly and cephabosporins, e.g. ceftazidime 50100 mg/kg per day, or cefotaxime 2 g 8-hourly. The use of these routines, the monitoring of subsequent wound infection and the alternation of combinations of chemotherapy should be monitored by the infection control team. It should not be forgotten, in treating postoperative pyrexial infection, that a failure to respond to a very broad spectrum of these combined antibiotics requires a critical bedside review to exclude collections of pus and other causes of a raised temperature. New antibiotics should be used with caution and, wherever possible, sensitivities should have been obtained. There are certain general rules from which the choice of antibiotics may be based originally; thus it is unusual for Pseudomonas aeruginosa to be found as a primary infecting organism unless the patient has had surgical or hospital treatment. Local antibiotic sensitivity patterns vary from centre to centre and from country to

country, and the sensitivity patterns of common pathogens will be known to the hospital microbiologist. Antibiotics used in treatment and prophylaxis of wound infection Antimicrobials may be produced by living organisms (antibiotics) or by synthetic methods. Some are bactericidal, e.g. penicillins and aminoglycosides, and others bacteriostatic, e.g. tetracycline and erythromycin. In general, penicillins act upon the cell wall and are most effective against bacteria that are multiplying and synthesising new cell wall materials. The aminoglycosides act at ribosomal bevel, preventing or distorting the production of proteins required to maintain the integrity of the enzymes in the bacterial cell. Penicillin. Florey and Chain produced the first therapeutic preparation in 1941, benzylpenicillin, which has proved most effective against Gram-positive pathogens including most streptococci, the cbostridia and some of the staphylococci which do not produce j3-lactamase. It is still effective against actinomycosis, which rarely is a cause of wound infection, and may be used to treat spreading streptococcab infections specifically, even if other antibiotics are required as part of therapy of a mixed infection. All serious infections, e.g. gas gangrene, require high-dose intravenous benzylpenicilbin, e.g. 1.2 g 4-hourly. Flucloxacillin and methicillin. These are beta-lactamaseresistant penicibbins and are therefore of use in treating staphybococcal 3-bactamase-producing organisms. This is the only reason for using them; and flucloxacillin has poor activity against other pathogens. Ampicillin and amoxyciblin. These 3-bactam penicibbins are absorbed orally or may be given parenterabby. Pharmacodynamically, amoxycilbin is superior. Both are effective against enterobacteriaceae, against E. faecalis and the majority of group D streptococci, but not species of Klebsiella or Pseudomonas. Mezlocillin and azlociblin. These are ureidopenicibbins with good activity against species of Enterobacter and Klebsiella. Azlocibbin is particularly effective against Pseudomonas. Each has some activity against Bacteroidesand enterococci, but each is susceptible to 13-lactamase. Combined with an aminoglycoside, mezlocibbin is a valuable treatment for severe mixed infections, particularly Gram-negative organisms in the immunocompromised patient. Klebsiella strains are best treated with mezlocillin, Pseudomonas strains with azlocillin. Clavulanic acid is available combined with amoxycibbin for oral treatment. This anti beta lactamase protects the amoxyciblin from inactivation by beta-bactamase-producing bacteria. It is of considerable value for treating Klebsiellastrains and beta-lactamaseproducing E. coli infections, but of no value against Pseudomonas strains. Sometimes it is used for locabised cebbubitis or superficial staphylococcal infection and should be used for infected human and animal bites. It is available for oral or intravenous therapy. Cephalosporins. There are many beta-lactamase-susceptible (not further considered here) and beta lactamase-stabbe cephalosporins available. There are three that find a place in surgical practice: cefuroxime, cefotaxime and ceftazidime. The first two are most effective in intra-abdominab skin and soft tissue infections, being active against S. aureus, and most enterobacteria. As a group, the enterococci (S. faecalis) are not sensitive to any of the cephalosporins. Ceftazidime, although being active against the Gram-negative organisms and, to a lesser extent, S. aureus, is most effective against P aeruginosa. These cephalosporins may be combined with an aminoglycoside, such as gentamicin, or an imidazole, such as metronidazole, if guaranteed anaerobic cover is needed.

Aminoglycosides. Gentamicin and tobramycin have similar activity and are particularly effective against the Gram-negative enterobacteriaceae. Gentamicin is effective against many strains of Pseudomonas, although resistance develops rapidly, but all aminogbycosides are inactive against anaerobes and streptococci. Serum levels immediately before and 1 hour after intramuscular injection must be taken 48 hours after the start of therapy, and dosage should be modified such that the trough level remains at or below 2.5 mg/litre and the peak level should not rise above 10 mg/litre. Ototoxicity and nephrotoxicity may follow sustained high toxic levels. They have a marked postantibiotic effect and single large doses are effective and may be safer. Vancomycin is most active against Gram-positive bacteria. It is ototoxic and nephrotoxic. Serum bevels should be monitored but this antibiotic has proved most effective against mubtiresistant staphybococcal infection and, when given oralby, it is effective against C. difficile in cases of pseudomembranous colitis. Metronidazole is the most widely used member of the imidazobe group and is active against all anaerobic bacteria. It is particularly safe and may be administered orally (up to 600 mg 8-hourly), rectally (up to 1 g suppository 8-hourly) or intravenously (500 mg 8-hourly). Infections with anaerobic cocci and strains of Bacteroidesand Clostridia are effectively treated or prevented by its use. Metronidazole is responsible for the reduction of anaerobic infections after abdominal, coborectab and pelvic surgery. Mention has been made of meropenem which, together with imipenem, is a member of the carbopenems, which are stable to beta-lactamase. They have useful broad-spectrum anaerobic as webb as Gram-positive activity but are expensive. The quinolones are potent microbicidab agents with action against Pseudomonas spp., e.g. ciprofloxacin. Their clinical robe in managing wound infection has not been defined. Further reading Cohen, I.K., Diegelmann, R.F. and Lindblad, WJ. (1992) Wound Healing. Biochemical and Chemical Aspects, WB. Saunders, Philadelphia, PA. Davis, J.M. and Shires, G.T. (1991) Principles and Management of Surgical Infections, J.B. Lippincott Co., Philadelphia, PA. Howard, R.J. and Simmons, R.L. (1988) Surgical Infectious Diseases, 2nd edn, Appleton and Lange, Norwalk, CT. Leaper, D.J. and Harding, K.G. (1998) Wounds: Biology and Management, Oxford Medical, Oxford. Majno, G. (1977) The Healing Hand. Man and Wound in the Ancient World, Harvard University Press, Cambridge, MA. Taylor, E.W (1992) Infection in Surg