Surgical infections and their management

Aims

The aims of this chapter are to:

• Define the terminology associated with infection.
• Describe the preoperative, intraoperative and postoperative factors that can lead to infection
• Detail the signs, symptoms and investigation of surgical infection
• Discuss which pathogens are likely to cause infection
• Provide a rationale for antibiotic prescription, whether as prophylaxis or after established

infection (either before or after microbiological diagnosis)

Objectives

After reading this chapter, you should be able to:

• Identify patients at risk of perioperative surgical infection
• Recognise and investigate the presence of infection in patients
• Make an educated guess as to which organisms are causing infection
• Treat the systemic manifestations of infection
• Formulate a rationale for ‘blind’ antibiotic therapy.

Introduction

Perioperative infection of the surgical patient is common. Lifestyle factors, such as diet and smoking, together with the presenting disease process (e.g. cancer), predispose patients to infection. Endogenous microbial colonisation of tissues can occur as a consequence of the course of a disease (e.g. perforation of an intra-abdominal viscus) or as a result of operative intervention. Exogenous infection of the patient may occur through non-sterile surgical technique or simply by failure to maintain an acceptable standard of cleanliness on wards or between each patient contact. The prevention of infection is of paramount importance and may be achieved by antiseptic/aseptic precautions, together with the judicious use of prophylactic antibiotics. The management of established infection involves general interventional care of the patient combined with antibiotic therapy. Occasionally, a surgical procedure may be required. Communication with, and the involvement of, microbiologists facilitate rational antibiotic therapy. Indiscriminate use of antibiotics can lead to both microbial resistance and superadded infection, resulting in increased mortality rates, particularly amongst immunosuppressed patients.

Some definitions

There is often confusion amongst medical practitioners over what is meant by the various terms used to describe infection and its systemic effects. Currently, the most commonly accepted definitions are those formulated by the American College of Chest Physicians and the Society of Critical Care Medicine (1992).

Infection. Microbial phenomenon characterised by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms.

Bacteraemia. The presence of viable bacteria in the blood.

Systemic inflammatory response syndrome (SIRS). The systemic inflammatory response to a variety of severe inflammatory insults. The response is manifested by two or more of the following conditions:

• Temperature outside the range 36-38⁰C
• Heart rate above 90 beats per minute
• Respiratory rate more than 20 breaths per minute, or PaCO₂ lower than 4.3kPa.
• White blood cell (WBC) count outside the range of 4 - 12 x 10⁹ per litre, or more than 10% immature forms

Sepsis. The systemic inflammatory response caused by infection i.e. the presence of the above physiological parameters in response to the presence of an identifiable infective agent.

Severe sepsis. Sepsis associated with organ dysfunction, hypoperfusion or hypotension. Hypoperfusion and perfusion abnormalities may include, but are not limited to lactic acidosis, oliguria, or an acute alteration in mental status. Hypotension describes a systolic BP of less than 90 mmHg or a reduction of more than 40 mmHg from baseline, in the absence of other causes for hypotension.

Septic shock. Sepsis with hypotension, despite adequate fluid resuscitation, along with perfusion abnormalities that may include, but are not limited to lactic acidosis, oliguria, or an acute alteration in mental status. Patients who are on inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured.

Multiple organ dysfunction syndrome (MODS). Presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

Note that the above definitions describe a progression of worsening disease from infection to MODS. Septicaemia, which inaccurately describes a wide range of infection and its pathophysiological consequences, has been abandoned in the terminology of infection.

In addition, several other definitions are used (Table 1:

Table 1 Definitions associated with surgical infection

Carrier	A person who has been colonised, but who does not manifest infection
Pathogen	An agent with the ability to cause infection
Endogenous infection	Infection of the body by natural host flora
Exogenous infection	Infection of the body by organisms not usually cultured from the host
Nosocomial infection	Infection acquired during hospitalisation
Virulence	The potential of a pathogen to cause infection

The pathophysiology of infection

Many pathogens normally reside in or on the human body without causing infection. For example, 35% of family members of patients with Neisseria meningitidis infection (meningococcal meningitis) have been found to be asymptomatic carriers. It has been estimated that the adult human intestine contains 2 kg of bacteria. In the non-diseased state a number of specific and non-specific mechanisms contribute to the host’s resistance to infection.

Non-specific mechanisms of immunity

There are a number of physical barriers that prevent host inoculation by pathogens. To gain entrance to the body, organisms must physically breach membrane barriers in the host, including the skin, respiratory tract, mucous membranes or urinary tract. In addition a number of non-specific host defences operate (see table 2).

Table 2. Non-specific host defences.

Behavioural factors	personal hygiene nutrition personal contact
Skin	fatty acids low pH
Tear production	tears contain antibacterial lysozyme and immunoglobulin A
Respiratory tract upper lower	coughing and sneezing mucociliary escalator bactericidal secretions secretory IgA macrophages
Gastrointestinal tract	stomach acidity enzyme production hepatic macrophages – Kuppfer cells secretory IgA
Urinary tract	urine flow urine acidity
Normal surface flora	competition for nutrients produce antimicrobial agents

Specific mechanisms of immunity

Specific mechanisms of immunity are those that have developed either artificially or naturally, through evolution. Artificial immunity may be provided passively or actively. Passive immunity involves injection of immunoglobulin or antiserum to provide immediate protection; immunity declines over the subsequent few months. Active immunity (vaccination) employs inactivated or attenuated organisms (or structural elements thereof) to induce the formation of antibody isotypes. A low intensity, short duration phase of antibody formation occurs during the month after vaccination. Subsequent exposure to the appropriate pathogen produces a rapid (3-5 days), larger and more sustained response to the infecting organism.

Similarly, natural immunity may be provided actively or passively. Passive natural immunity occurs due to maternal transplacental transfer of antibodies to the fetus and provides a degree of immunity for the newborn until 6 months of age. Active natural immunity involves a complex interaction between humoral (antibodies, complement), cell mediated (macrophages, T lymphocytes and B lymphocytes) and cytokine components.

Table 3. Host response to infection.

Non specific mechanisms	Specific mechanisms – immunity
Physical barrier Behaviour Secretions Natural flora	Artificial active --- vaccination passive --- immunoglobulin antiserum
	Natural active --- humoral --- cell mediated passive --- maternal transfer of antibodies

Infection, therefore, is likely to result when the host responses described above are bypassed, circumvented or absent, particularly by a more virulent organism.

Direct inoculation of pathogens into the bloodstream avoids non-specific host responses to infection. This may occur when barriers are absent or damaged:

· de-epithelialisation burns

trauma

· gross tissue damage burns

trauma

infection

surgery

· medical intervention intubation and ventilation

iatrogenic (intravenous access, inadvertent tissue damage)

drugs (eg H₂ antagonists)

· disease process perforation intraabdominal viscus

inflammation (pancreatitis, SIRS)

In addition, and less apparently, the structural and functional integrity of intact barrier mechanisms may be indirectly disrupted:

· alterations in antibiotic usage

natural flora nosocomial colonisation

malnutrition

use of bowel preparations

· damage to immobility and pressure necrosis of tissues

epithelial cells irradiation

chemotherapeutic cytotoxins

contact hypersensitivity (to dressings, skin

preparations)

· tissue ischaemia/anaemia

hypoxia

hypotension

reduction of arterial flow

· internal emboli

· external inflammation

cross clamping

Specific immunity may be compromised in several ways:

· overwhelming infection after gross inoculation

· genotypic factors

· immunosuppression cancer

malnutrition

drugs (immunosuppressants, steroids)

HIV infection

blood transfusion

There may exist considerable interindividual variation in response to bacteraemia. A cohort of patients undergoing the same surgery under similar conditions will exhibit a range of responses to surgical infection. Some patients will not develop infection. Others will exhibit mild infective signs but will recover. A minority may develop fulminant infection, leading to multiple organ failure and death. Both a reduction in major histocompatibility complex (MHC)-II expression by monocytes (which effect antigen recognition and presentation) and an excess of CD16 expression on neutrophils have been described in non survivors, implying that death after infection may occur as a result of both an underactive and an overactive immune response.

Preoperative considerations

There are a number of preoperative factors that may predispose patients to surgical infection. Their identification and treatment prior to surgery may greatly contribute to a reduction in the rates of infection and perioperative morbidity. Three groups of preoperative factors are recognised - coexisting diseases, surgical diseases and environmental factors.

Coexisting conditions

This group comprises chronic pathologies or behaviour exhibited by the patient prior to surgery.

Cardiovascular disease

Cardiovascular pathology may effect infection, inhibiting the body’s response to infection or limiting the ability of the patient to cope with physiological strain placed upon it by sepsis. Atherosclerosis, venous stasis and cardiac failure give rise to tissue ischaemia, which may be compounded by anaemia. Ischaemia may predispose to infection, inhibit humoral and cell mediated immune responses and delay recovery from infection. Pulmonary oedema attenuates non-specific lung immune responses. Damaged heart valves may become colonised during episodes of bacteraemia, resulting in bacterial endocarditis. During sepsis and MODS, ischaemic heart disease limits cardiac output, which worsens tissue ischaemia.

Respiratory disease

Chest infection is common following surgery, with an increased incidence amongst asthmatics and patients with chronic obstructive pulmonary disease (COPD). Patients who have surgery whilst suffering from an upper respiratory tract infection (or up to two weeks after the infection) have both an increased risk of airway complications during anaesthesia (coughing, laryngospasm) and postoperative chest infection; this is particularly true of children. Chest infection results in relative hypoxia, which can worsen wound healing, and may result in wound dehiscence after bouts of coughing.

Smoking

Smokers are at increased risk of perioperative surgical infection. Smoking is an airway irritant. It results in inflammation, disruption of ciliary function and increased production (with decreased clearance) of respiratory secretions. Chronically, alveolar fibrosis and emphysematous damage occur, disrupting immune and respiratory function. Carboxyhaemoglobin has 100 times greater affinity than oxygen for haemoglobin, resulting in reduced oxygen transport by haemoglobin. Ischaemia is worsened by smoke related increases in blood viscosity (due to hypoxia induced polycythaemia) and cardiovascular disease (atherosclerosis and coronary ischaemia). Immune function appears to be inhibited by some of the 4000 chemicals that have been identified in cigarette smoke together with lowered immunoglobulin levels and decreased leucocyte function.

Preoperative cessation of smoking should be strongly encouraged, preferably for more than 8 weeks before surgery. Carboxyhaemoglobin has a half-life of 4 hours; so even 24 hours cessation allows relative normalisation of haemoglobin oxygen carriage.

Obesity

Several definitions of obesity exist, but the most commonly used describes a person as obese if their body mass index (BMI) is more than 30. Approximately 33% of the population, therefore, are classed as obese. 1% of the population is morbidly obese – that is, they have a BMI of greater than 40.

Body mass index = weight (kilograms)

height (metres)²

The physiological stresses placed on the body by obesity lead to excessive perioperative morbidity and mortality. Perioperative infection is more common for several reasons:

· the obese have increased chest wall weight and a greater volume of intraabdominal contents. When placed supine, the compliance of their chest wall decreases, causing the functional residual capacity (FRC – the volume of air in the lungs after tidal expiration) to fall below the closing capacity (CC – the volume of air in the lungs when small airways begin to close). This leads to small airway closure, atelectasis and ventilation/perfusion mismatch, which is worsened by anaesthesia and neuromuscular blockade. Being unable to cough as effectively as thinner patients, they are therefore more prone to postoperative chest infections. In addition, the obese are more prone to gastro-oesophageal reflux, which may contribute to pulmonary colonisation by enteric organisms.

· the resultant hypoxaemia, together with the increased oxygen consumption and ischaemic heart disease associated with obesity, leads to relative tissue ischaemia and results in poor wound healing, with dehiscence and infection.

· suture lines are placed under abnormal strain in obese people resulting in wound dehiscence

· diabetes and abnormal glucose tolerance are more common in the obese and are worsened by the stress response to surgery, resulting in poor wound healing and urinary tract infection.

· pressure sores are more common. Hyperglycaemia and hypoxia play a role, but ischaemia due to body size is of primary importance. Consider two people, one with a body mass of 65kg (Patient A) and the other with a body mass of 130kg (Patient B). If they both have a sacral pressure area of approximately 20cm² (0.04m²), the pressure exerted over that area is:

Patient A: P = F = 65kg x 9.81N/kg = (approximately) 16,000 N/m²

A 0.04m²

= 16,000 Pascals = 16kPa : 16kPa x 760mmHg = 120mmHg

101.3kPa

Patient B: P = F = 130kg x 9.81N/kg = (approximately) 32,000 N/m²

A 0.04m²

= 32,000 Pascals = 32kPa : 32kPa x 760mmHg = 240mmHg

101.3kPa

therefore, if the systolic blood pressure of both patients is 130mmHg, blood will flow to the sacral pressure area of Patient A (as the blood pressure supplying the area is temporarily higher than the mechanical pressure exerted on the arterioles of the area by body mass) but will not flow to the sacral pressure area of patient B, resulting in tissue ischaemia and breakdown.

· increased adipose tissue predisposes patients to wound haematomas, which may become infected

· deeper skin folds produce warm, humid conditions for bacterial growth and facilitate bacterial entry to the body through friction damaged skin.

Malnutrition

In the Western world, malnutrition is an often under-recognised condition in patients presenting for surgery. The patient may be undernourished (a pure calorie deficiency) or inappropriately nourished (e.g. obtaining virtually all their calories through the intake of alcohol!). Several groups of patients are at greater risk of malnutrition: babies, the elderly, starved patients, alcoholics and patients with malabsorption, intestinal fistulae, chronic sepsis, previous GI surgery, cancer (particularly if undergoing chemotherapy or radiotherapy) or chronic liver disease. Hypercatabolism, associated with the stress response to surgery, further reduces the nutritional reserves of the patient. Malnutrition results in poor wound healing, increased muscle breakdown (predisposing the patient to chest infection) and reduced immune function.

Liaison with dieticians is important. Nutritional support in the perioperative period may be provided by supplemental use of nutritional drinks, nasoenteral feeding or parenteral nutrition (see Chapter 17).

The elderly

.

Old age is not per se an independent variable for perioperative infection, but a number of pathophysiological changes occur in the elderly that increase the likelihood of infection:

· reduced chest and lung compliance, raised closing capacity and reduced autonomic responses to hypoventilation predispose to chest infection

· atherosclerosis and reduced cardiac function lead to tissue ischaemia, with delayed wound healing, which may be worsened by anaemia

· increased incidence of occult malignancy

· obesity

· malnutrition and increased alcoholism

· reduced mobility

· reduced communication and reduced compliance with treatment

· increased periodontal disease

· thin skin

· impaired temperature regulation

· reduced immune function

Diabetes

In the perioperative period, several factors alter glycaemic control in the diabetic patient, including fasting, anxiety and the stress response to surgery. Diabetics are more prone to infection than non diabetics because:

· cellular immunity is reduced

· glycosuria and chronic renal failure predispose to urinary tract infection

· peripheral neuropathy reduces patient awareness of early infection (e.g. loss of pain sensation)

· autonomic neuropathy reduces sensitivity to hypoxia and hypercapnia, resulting in hypoventilation and reduced blood oxygen carriage. Autonomic neuropathy also produces gastric paresis with an increased incidence of aspiration pneumonia

Perioperative glycaemic control may be improved by the involvement of the diabetic team, and by using ‘sliding-scale’ short-acting insulin regimes, for both insulin dependent and non-insulin dependent diabetics (Chapter 4).

Steroids

Steroids, although invaluable in the treatment of autoimmune disease, organ transplants and inflammatory disorders, have several side effects that predispose patients to infection:

· altered body habitus and obesity

· thinning of the skin, increasing the likelihood of it being breached by minor trauma (e.g. removal of adhesive bandages) and delaying wound healing

· hyperglycaemia

· reduced immune function

· reduced fibroblast function, decreased fibrosis and decreased blood vessel proliferation

Despite these problems, steroid usage should continue throughout the perioperative period. Cessation may have two adverse effects. Firstly, the condition for which the steroids are being given may worsen; this may not be so problematic in the case of, for example, polymyalgia rheumatica, but can lead to significant morbidity, for instance, if it enables rejection of a transplanted organ. Secondly, chronic steroid administration causes adrenal suppression. Perioperative cessation of steroids could therefore render the patient less capable of dealing with the stress of surgery. Indeed, it may be the case that those on exogenous steroids require perioperative supplementation, particularly for more major surgery, because they are unable to produce the endogenous steroid surge required to enable the body to cope with trauma (Chapter 4).

Surgical conditions

Certain surgical pathologies predispose to perioperative surgical infection.

Gastrointestinal disease

The alimentary canal, from mouth to anus, is colonised with bacteria. Excessive translocation of bacteria from the gut lumen into the circulation or to surrounding tissue can occur quickly if the structural and functional integrity of the gut wall is breached, such as may occur with facial trauma, duodenal and diverticular perforation, or mesenteric infarction. Spillage of large bowel contents into the abdominal cavity bypasses the immune capacity of the liver, and bacteria may translocate into the circulation in the subphrenic area and paracolic gutters. Collection of blood, pancreatic secretions and bacteria can result in abscess formation, particularly in the subphrenic region. This may be prevented to a degree by thorough irrigation of the abdominal cavity, prior to closure.

Trauma

Soft tissue injury causes haematoma formation, oedema and tissue ischaemia, which provide ideal growth conditions for bacterial growth and replication. Skin damage promotes wound colonisation. Deeper infections may result due to blunt trauma and penetrating injury, particularly if inoculation of debris (such as clothing, bullets, skin) occurs. Severe trauma leads to massive endothelial damage, with the release of vasoactive substances and inflammatory mediators, resulting in multiple organ failure (MOF); sepsis is often coexistant (either secondary to the trauma itself or due to enteric bacterial translocation) and mortality is high.

Burns

Burns cause thermal damage to tissue, which has two effects. Firstly, the burnt tissue becomes ischaemic, due to blood vessel damage and oedema. A serosanguinous exudate is produced by skin that is partially burnt which acts as a growth medium for bacteria. Secondly, in a similar fashion to severe trauma, the massive endothelial damage associated with burns effects an inflammatory cascade that results in MOF. Large burns cause extreme hypercatabolism so malnutrition quickly ensues, as does hyperglycaemia, which both favour infection.

Environmental factors

Semmelweiss described asepsis in 1851. Lister described antisepsis in 1867. Both recognised that disease could be transmitted from one person to another; even if the carrier did not themselves show signs or symptoms of disease. Scrupulous hygiene on wards and amongst staff was the main method of infection control until the introduction of antibacterial agents (notably penicillin in the early 1940’s). Subsequent reliance on antibiotics to treat infection has produced a degree of indifference to maintaining standards of hygiene in hospitals. The recent evolution of multiply drug resistant bacteria, however, has reiterated the importance of antiseptic precautions.

The hospital environment

By the nature of their activity, hospitals are prone to the transmission of infection amongst patients. Intrapatient and interpatient infection may occur through patient/patient, patient/relation and patient/staff contacts, as well as through ventilation systems, washing and sanitary facilities. It is therefore prudent to minimise patient contact with the hospital environment: investigations and preoperative assessment may be carried out on an outpatient basis and the time between admission and surgery should be minimised. Patient transfer around the hospital and between hospitals should be avoided. The importance of handwashing (and the use of alcohol and glycerine skin lotion) by relatives and staff between patient contacts cannot be underestimated and is to be strongly encouraged. Appropriate protective clothing may be required to nurse some patients. Special areas or wards should be reserved for patients with established infection or particularly virulent forms of infection. Similarly, those patients at particular risk of infection (those with HIV or haematological malignancy) should be isolated onto special wards. An infection control team should be employed to coordinate the hospital’s infection policy.

The surgical list

Introduction

The order of the surgical list may need to be altered to account for operations or patients with a high risk of infection. Surgical procedures may be stratified into 4 classes, according to their potential for causing both infection and contamination of the surgical environment (see table 4).

Table 4. Classes of surgical procedure. (GU = genitourinary)

Parameter	Class of surgical procedure
	Class I	Class II	Class III	Class IV
GI, GU, tracheobronchial system integrity	Intact	Transection with minor spillage	Transection with major spillage Incision through infected tissue	Dead tissue, direct infection, pus
Sterile technique	Continuous	Minor lapses	Interrupted	Contamination despite sterile technique
Antibiotic prophylaxis	Not required	Single dose	Broad spectrum	Broad spectrum
Wound infection rate	1.5%	< 8%	12% 15-25% without antibiotics	> 25%
Surgical wound produced	Nontraumatic Uninfected	Mildly contaminated	Grossly contaminated	Contaminated with pus, faeces or extraneous material
Examples	Endocrine Orthopaedics Skin	Elective GI Dental Gynaecological	GI perforation Open fracture reduction	Abscesses Faecal peritonitis Trauma > 4 hours

The theatre environment.

Theatre design and the conduct of surgery and staff have been designed to minimise the likelihood of perioperative infection. These include:

List order

This is common sense and means putting a grossly infected patient on the end of the list rather than the beginning!

Area designation

The theatre environment becomes progressively more sterile from the ‘front door’ to the operating table. The patient initially passes from the ward to theatre reception, beyond which relatives should not be allowed to pass. From reception, or a holding area, they pass to the anaesthetic room. Accompanying ward staff should wear shoe coverings and hats during this transfer, and should leave shortly after handing over the patient. All theatre staff should wear surgical scrubs and theatre shoes, have their hair tied back under theatre hats and avoid the wearing of make-up or jewellery. Staff should never leave the theatre environment in surgical gear; if this is unavoidable, they should always change their scrubs before returning to theatre. Non-sterile non-surgical procedures, such as urinary catheterisation, should be carried out in the anaesthetic room, prior to transfer to the operating theatre. Likewise, blankets and extraneous items should be removed before entering the operating theatre.

Operating theatre design

Operating theatres are ventilated with positive pressure, clean and filtered air, that cycles from the patient to the periphery of the theatre. For most types of surgery, the air is recycled 20 times an hour. This may be increased to 40 times an hour in the case of prosthetic joint surgery, for which, specially designed compartmental airflow systems (e.g. Charnley®) may also be used. The design of entrances and exits is such that laminar airflow is correctly maintained, even when doors are opened. Three separate areas of the operating theatre exist: the operating room proper and the instrument preparation room, both of which are maintained highly sterile, and the scrub area. The operating theatre floor should be cleaned with antiseptic solution between each case, and is more thoroughly decontaminated and sterilised after each surgical list. Ideally, after ‘dirty’ cases a period of 30 minutes should elapse before commencing the next case, to allow sufficient time for airborne pathogens to be filtered. Separate areas external to the operating theatre are maintained for the disposal of waste, the storage of equipment and the cleaning of equipment.

Scrubbing

Correct scrubbing technique is essential to maintain a sterile field around the patient. The process should be taught and retaught to surgeons by theatre sisters. The surgeon should wear clean theatre dress, a theatre cap and a surgical mask. A gown pack is opened and surgical gloves placed, opened, next to it. Before the first patient of the list, a five-minute handwash should be performed, using Betadineâ or chlorhexidine. Nails should be scrubbed. The hands are dried, and the gown is put on followed by the gloves. A second person ties the surgeon into the gown. Between subsequent cases a two-minute hand wash is sufficient, providing the surgeon has not left the theatre environment in the interim, and has not just operated on a dirty case. Regloving is required: if the gloves are punctured, if a non-sterile area/person is touched, during long procedures, or during dirty procedures.

The patient

Ideally, the patient should be encouraged to shower before surgery. Shaving of the incision site may be required, but should be performed carefully to avoid microabrasions, which encourage infection. Once on the operating table (correctly positioned and prepared by the anaesthetist), the patient’s skin should be cleaned with antiseptic solution. Betadine or chlorhexidine are commonly used. Betadine should be applied for at least three minutes prior to incision; it has the advantage over chlorhexidine of clearly demarcating the area cleaned, but excites a higher incidence of allergic reactions. Cleaning should advance from the proposed site of incision outwards. Drapes are applied to leave the incision site exposed, but to cover every other part of the patient, which might come into contact with sterile personnel or equipment. Transparent, adhesive drapes are increasingly used to further limit patient skin exposure.

Adequate care should be taken during the procedure to maintain tissue perfusion and oxygenation. This is mainly the concern of the anaesthetist, who should endeavour to keep the patient normovolaemic, normotensive and normothermic, as well as protecting pressure points and reducing patient stressors (e.g. awareness and pain).

Surgical technique.

The practice of surgery has become considerably more refined with the passage of time – speed is no longer the only requirement of a good surgeon. Attention to intraoperative surgical technique can significantly hinder the development of perioperative infection. The following factors should be considered:

· Attire, scrub technique, patient preparation.

· Choice of technique. For instance, minimally invasive surgery reduces both tissue contamination by skin flora and the degree of tissue trauma. The infection of prosthetic material can be particularly disastrous; therefore, avoidance of prosthetics by the use of autologous tissue may be beneficial.

· Surgery of infected material. Adequate debridement of dead and infected tissue is required, together with irrigation (hence the surgical maxim ‘the solution to pollution is dilution’). Delayed primary closure or healing by secondary intention may be indicated. More esoteric treatments may be employed, including suction packing, hyperbaric oxygen therapy and the application of maggots.

· Haemostasis, closure and wound dressing. Haematomas provide an excellent growth medium for bacteria, so attention should be given to attaining haemostasis at surgery, particularly in patients with coagulopathy, cancer and chronic infection. Expansion of a haematoma may further compromise tissue blood supply. Drains may be used to prevent haematoma formation or the accumulation of infected/infectable fluids, but should be removed shortly after drainage of fluid ceases. Closure of the wound should aim to reconstitute normal anatomy, so as to prevent the formation of tissue dead spaces, in which seromata and bacterial multiplication might occur. Sutures should be applied in such a way as not to compromise the blood supply of the wound (thus avoiding wound breakdown). A range of suture material is available (e.g. natural and synthetic sutures, staples, self adhesive sutures and tissue glue) and the choice should be made according to the clinical indication. Sutures are removed, if necessary, once the skin has united. Dressings should be clean and applied without compromising blood supply. Postoperatively, dressings should be subject to regular inspection and replacement.

Diagnosis of infection

A number of clinical, haematological and microbiological variables may be assessed in order to both diagnose and monitor the course of an infection.

Wound inspection.

Infected wounds may be red, swollen, tender and hot (rubor, tumor, dolor and calor) due to the localised release of endogenous chemicals that cause vasodilation, increased membrane permeability and pain fibre sensitisation. The wound may extrude pus (which is predominantly composed of white cells), and may be malodorous. In addition, there may be a degree of dehiscence or tissue breakdown around drain sites. The efficacy of treatment may be observed by daily inspection of the wound.

Temperature

The wound itself may be hot. The patient may have a raised core temperature (above 37.5⁰C), due to the systemic release of pyrogens, such as interleukin-6, and the patient may be diaphoretic (sweaty) in an attempt to reduce their body temperature. Hyperpyrexia may lead to rigors, confusion, lethargy and tachycardia. Note that hyperpyrexia may occur in the perioperative phase without the presence of infection (e.g. stress response, post blood transfusion, drug reactions and malignancy), or due to an infection not associated with the wound (e.g. urinary tract infection, chest infection and venous line related sepsis. Swinging pyrexias are associated with abscess formation, low-grade pyrexia with wound infection (particularly if they occur around 5 to 6 days after surgery).

White cell count (WCC)

The WCC is most commonly raised in the presence of infection (i.e. greater than 11 x 10⁹ white cells/litre), with a marked predominance of neutrophils on the differential count. However, note that the white cell count may be either low or normal, particularly in immunosuppressed patients, leukaemic patients or occasionally when Gram-negative organisms infect the patient.

Other biochemical markers

C reactive protein (CRP – an acute phase protein) levels, erythrocyte sedimentation rate (ESR) and plasma viscosity may all be increased in the presence of infection. They are reasonably sensitive markers for infection but are very non-specific, and their use therefore is limited to monitoring the progress of treatment. CRP levels are mildly raised after surgery, decreasing to normal after 48 hours. The ESR and plasma viscosity may be normal after surgery depending on the degree of haemodilution.

Radiology

Radiological tests may be used as an adjunct to thorough clinical examination and appropriate simple investigations. X rays may be used according to the findings of the clinical examination (e.g. chest X-ray if a chest infection is suspected). Ultrasound scans may be used to detect collections of pus, though abdominal ultrasound is often technically difficult and may prove inconclusive in the presence of excess bowel gas or fat. Computerised tomography is an alternative to ultrasound scanning, but subjects the patient to a high degree of radiation exposure. A white cell scan uses radiolabelled white cells (indium 111-labelled leucocytes) to identify the site of infections that are difficult to diagnose clinically (e.g. osteomyelitis and vascular graft infection), although there is a real (but small) risk of HIV transmission with this technique.

Microbiology

Microbiological analysis of tissue specimens does not so much confirm the presence of infection as discover what the infecting organism is. Ideally, a specimen of pus or infected tissue should be sent – this may involve needle aspiration or operative retrieval of the specimen. Other samples to consider sending include blood, sputum, urine, faeces and drain contents. Samples should be sent before the commencement of antibiotic therapy. If the patient is already taking antibiotics, the type, dose and length of treatment should be written on the request form. Samples should be collected in a sterile manner to avoid false positive results due to cross contamination. Blood should be sent for microbiology, culture and sensitivities if the patient is systemically unwell. Blood should be taken in the normal sterile manner; an alcoholic swab should be used to clean the top of the culture bottles, the aerobic bottle being filled first, to avoid the inadvertent introduction of air into the anaerobic bottle. The results of a Gram stain are available within a few hours. Culture and sensitivity results take 24-72 hours. Immunological methods (for viruses) and more elaborate culture methods (e.g. for fungi and tuberculosis) may take longer.

Table 5. Classification of bacteria by Gram stain and morphology.

	COCCI	BACILLI
GRAM POSITIVE	Staphylococci Streptococci	Bacillus Clostridia Corynebacteria Listeria Mycobacterium
GRAM NEGATIVE	Neisseria	Pseudomonas Escherischia ) Yersinia ) Salmonella ) Shigella ) Enterobacteria Klebsiella ) Proteus ) Vibrio ) Haemophilus ) Bordatella ) Parvobacteria Brucella ) Serratia ) Campylobacter Bacteroides

Species of Spirochaetes, Mycoplasma, Legionella, Rickettsia, Coxiella, Chlamydia are termed ‘atypical’ because they are cannot be classified as either bacilli or cocci. They are Gram-negative organisms. Bacteria may be further sub-classified according to oxygen tolerance – i.e. aerobes, facultative anaerobes, or strict anaerobes.

Gram-staining imparts information concerning the cell wall of a bacterium. Gram-positive bacteria have a peptidoglycan cell wall that envelops the outer wall of the cell membrane. Gram-negative bacteria also possess a peptidoglycan cell wall (though it is thinner), but this is enveloped by an additional outer membrane with surface polysaccharide. This difference suggests that antibiotics that exert their effects on peptidoglycan cell walls, such as penicillins, will be less effective against Gram-negative organisms, in which the cell wall matrix has reduced exposure to antibiotic. Figure 1 gives an idea of the efficacy of various antibiotics.

Treatment

General principles

In general, the treatment of perioperative infection involves both the avoidance of cross infection with other patients and the tailored treatment of the specific infection affecting the patient. Cross infection may be avoided by barrier nursing, hand washing and use of alcohol and glycerine hand rubs between patient contacts, the use of sterile instruments and isolation methods.

Specific patient treatment involves careful clinical assessment, appropriate investigations, wound care, general treatment (e.g. fluid management, analgesia, physiotherapy, pressure area care), antibiotic treatment and reassessment.

Wound care

Ideally the wound should be kept scrupulously clean. Foreign debris (e.g. drains) should be kept to a minimum, and removed as soon as viable. The wound should be inspected daily and redressed in a sterile manner with an appropriate dressing:

· light exudates non-adherent gauze (e.g. Vaseline® dressing)

· heavy exudates hydrocolloid dressing

· mild slough hydrogel dressing

· heavy slough enzymatic desloughing dressing

· chronic slough vacuum sponge drain, larval therapy

The wound should be protected until healing is advanced, and the patient should be educated to avoid touching or picking at the wound. Topical antimicrobial agents or antiseptic washes may be employed.

Antibiotics

Without doubt, the discovery and use of antibiotics has saved many lives that would have otherwise been lost due to perioperative surgical infection. However, it is important to reiterate that they should only be used as an adjunct to general hygiene and antisepsis, due to the potential for development of bacterial resistance. There are a seemingly endless number of antibiotics from which to choose. Initially, it is often confusing to know which to use, as they vary in efficacy against different bacteria, in pharmaceutical preparation and in side effect profiles. The ideal antibiotic would be cheap, easy to produce, stable in a low-volume solution, available and effective in oral, intravenous and topical preparations, be bactericidal against Gram positive and negative rods and bacilli, spirochaetes and anaerobes, have a wide therapeutic range with minimal side-effects, be non-allergenic and resilient to the development of bacterial resistance.

In order to understand which antibiotics are appropriate treatment for which bacteria, it is helpful to classify bacterial species into 1 of 4 groups, depending on their morphology (bacilli or cocci) and acceptance of Gram stain (Gram-positive or Gram-negative, Table 5)

Figure 1 Efficacy of various antibiotics.

GRAM-POSITIVE

G

R

FA C 1

P

M

COCCI Me Ch BACILLI

C 3

T

C 2

Q A Te

GRAM-NEGATIVE

(R: rifampicin; FA: fucidic acid; G: glycopeptides; C1: 1^st; C2: 2^nd generation cephalosporins; C3: 3^rd generation cephalosporins; P: penicillins; M: macrolides; Me: meropenem; Ch: chloramphenicol; T: trimethoprim; Q: quinolones; Te: tetracyclines; A: aminoglycosides). For example, rifampicin (R) is more active against gram positive cocci, whereas aminoglycosides (A) are most effective against gram negative organisms, cocci and bacilli.

Atypical bacteria (Mycoplasma, Legionella, Rickettsia, Coxiella, Chlamydia) are best treated with tetracyclines, spirochaetes with penicillin. Anaerobic bacteria are killed by metronidazole.

Antibiotic prophylaxis

Prophylactic antibiotics reduce the rate of postoperative infection after procedures that produce bacteraemia or wound contamination, and in susceptible patients (e.g. those with valvular heart disease, the immunocompromised, and patients receiving prosthetic implants). Prophylaxis alone does not prevent infection, but forms part of the general anti-infection measures taken in the perioperative period.

A number of broad spectrum antibiotics are used, their choice being dependent on the type of surgery, the likeliest source of bacterial contamination, patient factors (e.g. allergy) and local or regional antibiotic policy. Prophylactic antibiotics are usually administered as a single dose prior to the operation, the aim being to have a high circulating concentration of antibiotic at the site of skin incision (they should therefore be administered at least 5 minutes prior to application of a tourniquet). Prophylaxis may be carried on into the immediate postoperative phase (up to 24 hours) after which continued administration is classed as therapeutic. Commonly used prophylactic regimes are shown in table 6.

Table 6 Commonly used prophylactic antibiotics.

Type of surgery	Likely infecting organism	Prophylactic antibiotic
Cardiac	S aureus Coagulase negative staphylococci	Cefuroxime 750mg iv or Vancomycin 15mg/kg iv (if cephalosporin sensitive)
Vascular
Prosthesis placement
Neurosurgery
Thoracic
Orthopaedic
Gastrointestinal	G- bacilli, S aureus S faecalis Anaerobes	Cefuroxime 750mg iv + Metronidazole 500mg iv +/- Gentamicin 5mg/kg iv (3mg/kg in renal disease)
Obstetric/gynaecological	G- bacilli, S aureus Group B streptococci Anaerobes
Head and neck (including dental)	S aureus Streptococci Anaerobes
Urological	Gram – bacilli S faecalis	Gentamicin 120mg iv Amoxycillin/clavulanic acid 1.2g iv

Specific antibiotic therapy

There is inevitably a delay between taking a microbiology sample and obtaining a culture and sensitivity result. Therefore, the initial treatment of perioperative infections necessitates an empirical, 'best guess' approach to antibiotic treatment.

This is based on:

· clinical assessment of the most likely infecting organism (according to the type of surgery and the site of infection)

· the severity of the infection

· Gram stain results

· local antibiotic policies

· patient factors (allergy, renal impairment, recent antibiotic administration).

Common empirical regimens include:

· minor surface infections narrow spectrum: flucloxacillin (if S aureus) suspected

broad spectrum: cefuroxime

· chest infection penicillins

· after GI surgery cefuroxime + metronidazole +/- gentamicin

+/- antifungal

· after urological surgery co-amoxiclav, gentamicin

· severe sepsis vancomycin + gentamicin + metronidazole

· MRSA vancomycin

· vancomycin resistant consult microbiologist

enterococcus (VRE)

· Pseudomonas suspected ciprofloxacin

Subsequently, therapy should be guided by the appropriate antibiotic sensitivities obtained after microbiological culture. The main types of antibiotics currently used are listed in table 5.

Table 7. The main groups of antibiotics.

Antibiotic	Site of action	Effective against	Side effects
Beta-lactams (penicillins, cephalosporins)	Bacterial cell wall	Broad spectrum or narrow spectrum	Hypersensitivity Nausea, vomiting, diarrhoea (NVD)
Antimetabolites (sulphonamides, trimethoprim)	Bacterial tetrahydrofolate production (à purine synthesis)	Urinary infections	Blood dyscrasias Rashes
Glycopeptides (vancomycin, teicoplanin)	Bacterial cell wall	Severe G+ infections	Blood dyscrasias Renal impairment
Quinolones (e.g. ciprofloxacin)	Bacterial DNA gyrase	G- infections Pseudomonas	NVD Cytochrome P450 inhibition
Rifampicin	Bacterial DNA dependant RNA polymerase	G+ cocci Mycobacteria	Liver enzyme induction Deranged LFTs Orange urine
Protein synthesis inhibitors Macrolides (erythromycin) Chloramphenicol Tetracyclines Aminoglycosides (gentamicin)	) Bacterial ) 50S ribosomal ) subunit ) ) Bacterial ) 30S ribosomal ) subunit )	G+ cocci Bacilli G- bacteria (esp. gynae flora) G- organisms	NVD Cholestatic jaundice Blood dyscrasias Grey baby syndrome Adsorbs onto growing bones and teeth Ototoxicity Nephrotoxicity
Metronidazole	Forms high energy bactericidal free radicals due to low redox potential	Anaerobes	NVD Antabuse effect Taste Neuropathy
Azole antifungals (e.g. fluconazole)	Fungal membrane	Yeasts Candida	Mild liver enzyme induction
Polyene antifungals (e.g. amphotericin B)	Membrane sterols (bacteria and humans)	Many fungal species	Deranged K, Mg and LFTs Nephrotoxicity Anaemia NVD

Antibiotic resistance

Bacteria may be naturally resistant to antibiotics, or may acquire immunity by a number of mechanisms. What is clear, however, is that antibiotic resistance is increasing: species that were formerly sensitive to certain antibiotics have mutated into resistant forms. Examples include methicillin (i.e. penicillin) – resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). The development of antibacterial resistance is primarily due to the indiscriminate use of current antibiotics, such that inadequate doses of broad-spectrum antibiotics are being administered for an inadequate time period.

Natural bacterial resistance may occur due to:

· natural impermeability to antibiotic molecules

· a lack of target binding sites

· lack of a target metabolic pathway

· the production of antibiotic destroying enzymes (eg beta lactamases)

Combinations of beta lactam antibiotics with beta-lactamase inhibiting drugs (e.g. amoxicillin + clavulanic acid – co-amoxiclav) may be effective against beta lactamase producing bacteria.

Acquired resistance may result from:

· alteration in cell wall/membrane permeability

· alteration in target binding site (e.g. penicillin resistant S pneumoniae)

· alteration in metabolic pathway (e.g. trimethoprim resistance)

· gene activation to produce antibiotic destroying enzymes (e.g. aminoglycoside resistance)

· New gene acquisition to produce antibiotic destroying enzymes

HIV infection

The human immunodeficiency virus is a retrovirus that infects CD4 (helper) lymphocytes (amongst others), with the result that cell-mediated immunity to infection is compromised. Up to 30,000 people are infected with HIV in the UK, a third of whom remain undiagnosed. 1.3% of the hospital patient population is infected with HIV. People with HIV infection are surviving longer due to earlier diagnosis and effective antiretroviral therapy. However, antiretroviral therapy, usually taken as a combination (‘triple therapy’) of two nucleoside analogues and a protease inhibitor (e.g. zidovudine – AZT), can have marked side-effects including pancreatic, hepatic and renal dysfunction, peripheral neuropathy, bone marrow suppression and gastrointestinal disturbances, all of which may debilitate the patient prior to operation.

The normal CD4 count is 0.6-1.5 x 10⁹ cells/l, but falls progressively after infection. Symptomatic disease typically occurs below 0.2 x 10⁹ cells/l, and is associated with susceptibility to opportunistic and postoperative infections (the latter occurring in up to 60% of cases). Opportunistic infections may include bacteria, viruses (especially herpes simplex (HSV) and varicella zoster (VZV) viruses, and cytomegalovirus (CMV)), fungi and protozoa, and there is a greater risk of these being multi-drug resistant. Immunosuppression may be further worsened by major surgery, anaesthesia, malnutrition, malignancy, concurrent organ failure and drug abuse.

Table 8. Potential postoperative infections in HIV infected patients.

Site of sepsis	Causative organisms
Superficial wounds/venous access	S aureus, S epidermidis, Coliforms, Bacteroides spp, Psuedomonas aeruginosa, HSV, VZV
Deep wounds/prostheses	S aureus, S epidermidis, Coliforms, Bacteroides spp
Respiratory tract	S aureus, Pneumocystis carinii, Mycobacterium tuberculosis, S pneumoniae, Legionella pneumophilia, fungi
GI tract	Coliforms, Bacteroides spp, Pseudomonas aeruginosa, Candida albicans, Cryptosporidium parvum, Clostridium difficile
Urinary tract	Coliforms, Enterococci
CNS	CMV, HSV, Toxoplasma gondii, Cryptococcus neoformans
Septicaemia	All of the above organisms, if immunosuppression is severe

HIV infected patients may present for any type of surgery. In the absence of any ethical or practical screening programme, all hospital patients undergoing surgery are effectively treated as if they might be infected - that is, universal precautions are employed for every patient. These precautions include:

· avoidance of contact between the patients’ body fluids and healthcare workers’ skin or mucous

membranes (gowns, gloves, masks/goggles, avoidance of hollow needles and aerosolisation of

fluids)

· use of electrocautery, blunt dissection and stapling guns, instead of scalpels and sutures

· use of intermediate receptacles for the handling of sharps

· guidelines for splash or direct inoculation injuries

All doctors are obliged to avoid infecting themselves and others. Surgeons and anaesthetists should seek advice perioperatively from HIV specialists and microbiologists. In addition, doctors should adopt practices which reduce exposure of the patient to opportunistic infections. Measures include the use of skin preparation and scrupulous aseptic technique, microbiological screens prior to surgery, prophylactic antibiosis and early treatment of suspected infection and appropriate perioperative isolation procedures including barrier nursing. Surgery may be deferred until the patient overcomes a concomitant infection, or until the CD4 count has recovered to an appropriate level (e.g. above 0.5 x 10⁹ CD4 cells/litre for contaminated surgery).

Postoperative pulmonary infections may be reduced by the appropriate use of regional anaesthesia, together with chest physiotherapy and early mobilisation.

The risk of transmission of HIV from a patient to a health care worker is reported as 1/450,000 to 1/1.3 billion. The risk of transmission of HIV from an infected surgeon to a patient is 1/130,000. Approximately 6/100 operations are associated with percutaneous injury to the surgeon. The seroconversion rate after percutaneous exposure is 0.3%. The following flow chart (Figure 2) details the course of action to be taken by a health care worker after suspected inoculation from an HIV infected patient (PEP = post-exposure prophylaxis).

Figure 2 The course of action to be taken by a health care worker after suspected inoculation from an HIV, hepatitis B or C infected patient (HBIG = hepatitis B immune globulin, PEP = post-exposure prophylaxis).

(Source for copyright, World Organisation of Gastroenterology website http://www.omge.org/guides/guideline2.htm#action)