Infections and antibiotics

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4 Infections and antibiotics

Importance of infection

In the latter half of the 19th century Louis Pasteur hypothesized that bacteria caused infection by being carried through the air (germ theory of disease). Aware of Pasteur’s work, in 1865, Joseph Lister first used carbolic acid (phenol) as a spray in the operating theatre to successfully prevent and treat infection in compound fractures. In the early part of the 20th century, with the advent of sterilized instruments, surgical gowns and the first rubber gloves, antisepsis was replaced by modern aseptic surgical techniques which were championed by Birmingham surgeon Robert Lawson Tait. Penicillin was discovered by Alexander Fleming in 1928 and first used clinically in 1940 by Howard Florey. The prevention and treatment of surgical infection was further transformed by the many different classes of antibiotics that were discovered through the latter part of the 20th century. Nevertheless, control of infection in surgical practice remains an important and challenging issue due to the emergence of antibiotic-resistant organisms and the rise in the numbers of elderly, co-morbid and immunocompromised patients undergoing increasingly complex surgical interventions that frequently involve the use of implants. The risk of infection is related to the type of surgery (Table 4.1). Postoperative infections impact on patient outcomes and increase the length of hospital stay, which in turn increases the cost of surgery. In the UK, there is now a legal duty on hospitals to do all they can to minimize the risk of healthcare associated infections (HCAI) in patients.

Table 4.1 Classification of operative wounds and infection risk with prophylaxis

  % Infection rate with prophylaxis*
Clean
(e.g. non-traumatic wound, respiratory / gastrointestinal /genitourinary tracts intact)
0.8
Clean-contaminated
(e.g. non-traumatic wound, respiratory / gastrointestinal /genitourinary tracts entered but insignificant spillage)
1.3
Contaminated
(e.g. fresh traumatic wound from dirty source, gross spillage from gastrointestinal tract or infected urine/bile or major break in aseptic technique)
10.2

* Based on data from: Olson M, O’Connor M, Schwartz ML. Surgical wound infections. A 5-year prospective study of 20,193 wounds at the Minneapolis VA Medical Center. Ann Surg. 1984 Mar;199(3):253–259.

Biology of infection

Many body surfaces are colonized by a wide range of micro-organisms, called commensals, with no ill effects (Fig. 4.1). However, once the normal defences are breached in the course of surgery, such as skin (e.g. Staphylococcus aureus) and bowel (e.g. Bacteroides spp. and Escherichia coli) commensals can then cause infection. Infection is defined as the proliferation of micro-organisms in body tissue with adverse physiological consequences. The factors involved in the evolution of infection are shown in Figure 4.2.

Host defence systems

Commensals limit the potential virulence of pathogens by depriving them of nutrients, preventing their adherence and by producing various cell signalling substances that interfere with their activities. Administration of broad-spectrum antibiotics can lead to the replacement of commensals with a pathogen; for example, Clostridium difficile in the colon which is a common cause of, potentially life threatening, diarrhoea in postoperative patients.

Man has evolved a wide range of defences that act at the interface with the surrounding environment. Skin provides a dry, inhospitable mechanical barrier to organisms and also secretes fatty acids in the sebum that kill or suppress potential pathogens. Tears and saliva contain a range of antibacterial substances such as lysozyme; and the low pH of gastric secretions kills many ingested pathogenic bacteria. Many mucosal surfaces are covered in secreted mucus which both acts as a physical barrier and binds bacteria via specific receptors.

Macrophages, neutrophils and complement provide innate immunity through phagocytosis and bacterial lysis. The complement system (a cascade of bioactive proteins) which is activated when required attracts the phagocytic cells, directly lyses pathogens and increases vascular permeability. Immunity can also be acquired through antibody and cell mediated mechanisms. There are two types of T-lymphocytes involved in cell mediated immunity; CD4 help macrophages kill phagocytosed bacteria and CD8 kill cells infected with intracellular pathogens, especially viruses. The five classes of antibody (IgA, IgM, IgG, IgD and IgE) are secreted by B-lymphocytes, usually following stimulation via T cells. Antibodies, with or without complement, bind to and opsonize, lyse or kill the pathogen.

Cytokines (small peptide molecules) are released by leucocytes and facilitate the interaction between immune cells. Over activation of this cytokine cascade leads to the Systemic Inflammatory Response Syndrome (SIRS). Typically, a patient presents with signs of severe infection but instead of improving with antibiotic treatment develops worsening fever, hypotension, tissue hypoxia, acidosis and multiple organ failure.

A number of host factors make infection more likely:

Preventing infection in surgical patients

All UK hospitals now have infection prevention programmes which include measures to minimize risks to patients and staff from infections which may be acquired during and after surgery.

Preoperative MRSA screening

Since 2008 hospitals in England have been required to screen all elective surgical patients for methicillin-resistant Staphylococcus aureus (MRSA). Carriers receive decolonization treatment (nasal mupirocin cream and antiseptic skin wash) and appropriate antibiotic prophylaxis, usually a glycopeptide antibiotic (e.g. teicoplanin) prior to surgery. This policy reduces MRSA transmission in surgical wards (EBM 4.1). Screening for nasal carriage of Staphylococcus aureus followed by decolonization also reduces surgical wound infection (EBM 4.2). These hospitals now screen emergency admissions although the timing of available results will determine whether this has an impact on management and outcomes.