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.

Prophylactic use of antibiotics

Antibiotic prophylaxis is defined as their use before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. The evidence base and guidance can be found at www.sign.ac.uk/pdf/sign104.pdf and in the British National Formulary (BNF).

Management of surgical infections

Surgical infections are of two types; those that occur in patients who:

Diagnosis

Infections in the early postoperative period (< 48 hours) are most likely to be respiratory or urinary; wound infections usually becoming evident later. Implant-related infections may not be evident for weeks, months or even years. Leakage of a gastrointestinal anastomosis usually presents after 5–6 days with low grade pyrexia and abdominal symptoms and signs; there may also be leakage of bowel content from surgical drains. Questioning for cough, dysuria and abdominal pain is important. Tachycardia, tachypnoea and pyrexia are all indicators of infection. Should hypotension and signs of septic shock be present, urgent resuscitation and assessment by the critical care unit outreach team is required. Whenever possible, the focus of infection should be identified (e.g. plain x-ray, ultrasound, computed tomography, (CT), or magnetic resonance imaging, (MRI)) and cultures taken (e.g. urine, sputum) before commencing antibiotic treatment. Aspiration of pus from deep seated infections (e.g. subphrenic abscess) followed by Gram staining to guide empirical therapy is helpful. Intravenous lines should be removed and cultured together with blood in any patient suspected of having bacteraemia. If indicated, urine and sputum should also be cultured. Serious sepsis in the surgical patient often arises from intra-abdominal infections (IAI). Approximately 30% of patients admitted to the ICU with IAI die, and if peritonitis develops mortality rises to 50%. Early diagnosis and treatment is essential but clinical examination is often unreliable, even misleading. CT, or MRI, preferably with contrast, should be performed to detect peritoneal leaks and collections of pus and can be life-saving. An integrated and logical approach to patient management should be followed as described in the surviving sepsis guidelines which are summarized in Tables 4.2 and 4.3.

Table 4.2 Screening for sepsis and severe sepsis

Are any two of the following present?

If yes: Does the patient have a history or signs suggestive of a new infection? If yes, patient has SEPSIS Are there any signs of organ dysfunction? NO: Treat for SEPSIS: YES: Patient has SEVERE SEPSIS Start
SEVERE SEPSIS CARE PATHWAY
(Table 4.3)

WCC, white cell count; MAP, mean arterial pressure, SBP systolic blood pressure; INR, international normalized ratio; APTT, activated partial thromboplastin time.

http://www.survivingsepsis.org/

Table 4.3 Severe sepsis care pathway

Plus

http://www.survivingsepsis.org/

Antibiotic therapy

Antibiotics are almost inevitably an adjunct to surgical treatment in surgical infections e.g. drainage of abscesses, debridement, excision of infected tissue or lavage of a serous cavity.

Table 4.4 Principles underlying antibiotic policy

Table 4.5 Antibiotics in surgery: suggestions for specific therapy

Organism First choice Alternative
Methicillin-sensitive Staphylococcus aureus (MSSA) Flucloxacillin Clarithromycin
Methicillin-resistant Staphylococcus aureus (MRSA)* Vancomycin Linezolid
Daptomycin
Coagulase-negative staphylococci Vancomycin Linezolid
Daptomycin
Streptococcus pneumoniae Benzylpenicillin Clarithromycin
Streptococcus pyogenes (group A β-haemolytic streptococcus) Benzylpenicillin
Clindamycin
Clarithromycin
Enterococci Amoxicillin Vancomycin
Bacteroides species Metronidazole Co-amoxiclav
Escherichia coli

Piperacillin-Tazobactam
Trimethoprim
Meropenem
Co-amoxiclav
Haemophilus influenzae Amoxicillin Co-amoxiclav
Klebsiella spp Co-amoxiclav Meropenem
Proteus species Co-amoxiclav Meropenem
Pseudomonas aeruginosa Piperacillin-Tazobactam Meropenem
Clostridium spp Benzylpenicillin + metronidazole Metronidazole
Clostridium difficile Stop predisposing antibiotic
Metronidazole
Vancomycin, oral, re-treat relapse

These suggestions should be considered in the light of local epidemiology, sensitivities, drug availability, site and severity or infection.

* Gould FK et al. Guideline (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J. Antimicrobial Chemotherapy 2009;63:849-861

Table 4.6 Empirical therapy for acute infections

Type of Infections Antimicrobial Alternative
Chest infection
Uncomplicated
Community-acquired pneumonia
‘Aspiration’ pneumonia
Hospital-acquired/postoperative
Amoxicillin
Benzyl penicillin + clarithromycin
Co-amoxiclav
Piperacillin-tazobactam
Clarithromycin
Levofloxacin + clarithromycin
Levofloxacin + metronidazole
Meropenem + vancomycin
Urinary tract infection
‘Lower’ infection
Acute pyelonephritis
Prostatitis
Trimethoprim
Co-amoxiclav
Ciprofloxacin
Amoxicillin
Gentamicin
Wound infection
Cellulitis
Abscess
Penicillin + flucloxacillin
Drain collection
Clarithromycin
Flucloxacillin
Intra-abdominal sepsis Amoxicillin + metronidazole + gentamicin Meropenem
Cholecystitis-cholangitis Co-amoxiclav Meropenem
Pelvic inflammatory disease Azithromycin + metronidazole + gentamicin Doxycycline + piperacillin-tazobactam
Amputations and gas gangrene Benzylpenicillin + metronidazole Metronidazole
Septicaemia and septic shock Amoxicillin + metronidazole + gentamicin/ciprofloxacin Piperacillin-tazobactam, meropenem
Severe Pseudomonas infections Piperacillin-tazobactam + gentamicin Meropenem ± gentamicin
Candida sepsis Fluconazole Caspofungin

Note The suggestions are for occasions when immediate treatment is necessary. Amendments may be necessary in the light of local epidemiology.

Specific infections in surgical patients

Surgical site infection (SSI)

All surgical wounds are contaminated by microbes but in most cases infection does not develop because of innate host defences. A complex interplay between host, microbial, and surgical factors ultimately determines whether infection takes hold and how it progresses (Fig. 4.2, EBM 4.3 and see Table 4.1).

Clostridium difficile infection (CDI)

This occurs when the normal colonic microflora is disturbed by the administration of antibiotics in patients either pre-colonized with or exposed after antibiotic treatment to C. difficile (an anaerobic spore-forming bacillus). Some antibiotics are particularly prone to cause CDI: clindamycin (the first identified in 1978), cephalosporins and fluoroquinolones. The disease is much more common in the elderly and in hospitals with poor cleaning. The bacterium produces two cytotoxins A and B (some strains only produce B) that destroy the colonic mucosal cell cytoskeleton. A spectrum of disease is seen ranging from abdominal discomfort to profuse watery diarrhoea (one of the commonest features), severe abdominal cramps and rarely toxic dilatation of the colon leading to rupture. At colonoscopy characteristic yellow plaques, bleeding mucosa and islands of normal tissue are seen, which is called pseudomembranous colitis. Surgical patients can acquire CDI as a consequence of antibiotic treatment or prophylaxis. Infrequently patients with severe CDI may require urgent surgical referral. Emergency colectomy in patients with fulminant colitis can be life saving although mortality is high. Diagnosis of CDI is by identification of the toxins in faeces by enzyme immunoassay (EIA) or the more sensitive and specific PCR detection of the toxin genes. Treatment of mild/moderate disease is with oral metronidazole, with severe disease responding better to oral vancomycin. Control is aimed at isolating patients with diarrhoea, reducing the environmental burden of spores by cleaning with bleach solutions and reducing the selective pressure from high risk antibiotics by antibiotic stewardship. Current UK guidelines are available in the document ‘Clostridium difficile – how to deal with the problem’ (www.dh.gov.uk); (www.hpa.org.uk).

Infections of prosthetic devices

In many fields of surgery the use of implants has become routine and affords huge clinical benefit. Nevertheless, there is a small risk of device-related infection which can be catastrophic for the patient. Bacteria, often commensals such as coagulase-negative staphylococci can be introduced at the time of surgery and form a biofilm of extracellular material (glycocalyx) around the device which is resistant to the body’s defences and the penetration of some antibiotics. Alternatively, the implant can be ‘seeded’ via the bloodstream months, even years, later from a bacteraemia arising from another source e.g. Staphylococcus aureus skin sepsis or E. coli UTI. Antibiotics alone are often unsuccessful and removal of the device is frequently necessary to eradicate the sepsis. Such surgery may be difficult and associated with significant morbidity and mortality.

Infections primarily treated by surgical management

Healthcare associated infections (HCAI)

In 2006 a survey of 190 acute hospitals in England showed that 8.2% of patients had developed a HCAI (previously known as a nosocomial infection), most commonly SSI, GI infections, UTI, and pneumonia. The UK Health Act of 2006 (revised 2008) places a legal duty on hospitals to do all they can to minimize the risk of HCAI. The hospital infection control team are most closely involved in the design and delivery of the HCAI programme and will liaise with the microbiology laboratory to ensure that infections caused by important pathogens are identified at an early stage and that trends in antibiotic resistance are monitored. However, all staff members and students have a duty to take responsibility for this very important aspect of patient care. In recent years, there has been a national focus on reducing MRSA and C. difficile infections in England using a multi-faceted approach; Figure 4.7 shows the successful reduction in England of MRSA bloodstream infections (bacteraemia) from 2006 to 2010 but continuing high levels of MSSA bacteraemia. Monitoring SSI is also an important quality indicator. The Nosocomial Infection National Surveillance Service (NINSS), a national programme of SSI surveillance, was established in the UK in 1997. Participation in the scheme is voluntary (except for orthopaedic surgery) but provides hospitals with useful benchmarking data for the main types of surgery. This systematic collection of infection data (surveillance) is by nurse follow-up of all patients who have undergone surgery during a given period. Surveillance nurses will inspect surgical wounds for any signs of infection and often also follow-up the patient once discharged home to detect infection. This enables the early identification of increased incidences of infection so that measures can be taken to prevent further infections. These measures could include suspension of further surgery; deep cleaning of theatres; change in antibiotic treatments and isolation of infected patients.