Infections and antibiotics

Human biology and microbiology

Having an understanding of common bacteria and fungi encountered in surgical practice can assist the practitioner in interpreting microbiological investigations ( Tables 6.3 and 6.4 ). Where particular organisms are isolated may significantly change infection control precautions (transmission-based precautions) or the treatment plan. Furthermore, awareness of not only infective complications of surgery but also the causative organism may lead to identifying the need to change surgical practice. For example, rising surgical site infection (SSI) rates or repeated isolation of less commonly encountered or particularly resistant bacteria should prompt reflection on whether best practice is being followed.

Bacterial resistance to antibiotics

Bacterial resistance to antibiotics is a phenomenon seen naturally in the environment. Use of antibiotics in human health, veterinary practice and agriculture has promoted the speed at which resistance has developed. Drug-resistant bacterial and fungal isolates are associated with worse clinical outcomes and increased healthcare costs.

Bacterial resistance can be intrinsic or acquired. Some of the more commonly encountered intrinsic resistance mechanisms include inability of the antibiotic to access the active site within the bacterial cell or being efficiently removed from the bacterial cell by an efflux pump. Acquired resistance occurs when mutations occur in chromosomal genes or when bacteria acquire new genes, e.g., plasmids allowing gene transfer between bacteria and bacterial species.

Acquired resistance mechanisms include:

• Further reduction of the concentration of the antibiotic within the bacterial cells through reducing access (porin loss) or increasing efflux

• Modification of the antibiotic target

• Inactivation of the antibiotic through hydrolysis or other enzymatic modification of the antibiotic.

Resistance in Enterobacteriaceae, e.g., Escherichia coli and Klebsiella spp, has become a worldwide problem that affects nearly all aspects of healthcare including the ability to practice surgery. A number of resistance mechanisms can be seen, but one of the more commonly encountered mechanisms is the production of enzymes that hydrolyse some antibiotics, e.g., beta-lactamases and carbapenemases. Refer to Table 6.5 for the terms used in bacterial resistance and Fig. 6.3 for changes in resistance patterns over time in Staphylococcus aureus and Enterococci spp.

Host defences and immunology

Structural barriers to infection include the skin and mucosal surfaces. Commensal organisms can prevent pathogens adhering to these surfaces, limit nutrient availability and produce chemicals such as mucus that interferes with the activities of or physically trap pathogens. Secretions prevent infection such as lysozyme in tears, acidic gastric secretions and proteins in urine to reduce the number or ability of pathogens to cause disease.

The immune system can be separated into the innate and adaptive immune system or cellular and humoral components. Pathogens are recognised by the innate immune system through pathogen-associated molecular patterns. Phagocytes use pathogen recognition receptors on their surface, such as the Toll-like receptor family. These receptors recognise different pathogen-associated molecular patterns such as peptidoglycan, flagellin or fungal proteins. Phagocytes include macrophages that can either be resident within tissues or derive from circulating promonocytes released from the bone marrow.

Neutrophils, another type of phagocyte with a shorter lifespan, are recruited into tissues when required. The stimulus from pathogen recognition receptor activation leads to a cascade of both cellular and humoral aspects of the immune response that result in an acute inflammatory process. This can include the complement cascade and release of acute phase proteins including interferons, interleukins and tissue necrosis factor. This leads to further immune cells being recruited into tissues and also cells (regulatory T cells) and molecules (interleukin-10), which moderate the immune response to prevent harmful tissue damage and overwhelming triggering of the host immune response. Other mechanisms for recruiting inflammatory cells include tissue damage, such as a skin breach during surgical procedure, which can release tissue factor as a trigger for the immune system.

The adaptive immune system has both humoral (antibodies produced by plasma cells derived from B lymphocytes) and cellular (T lymphocytes) aspects. These aspects are individually targeted to a pathogen and may take time to form a strong immune response. B cells often require the support of T cells to present antigens and set up an effective antibody response. T cells that have CD4 markers support macrophage intracellular pathogen destruction or support B cells to make antibodies. CD8 T cells are cytotoxic and kill cells infected with viruses.

Microbiological diagnostics in surgical practice

Microscopy and culture of biologic specimens remain key tools in the identification of pathogens to allow targeting of antimicrobial therapy. Routinely taking samples from patients with surgical infections enables targeted antimicrobial therapy and also builds up a pattern of antimicrobial resistance for commonly encountered pathogens. Understanding resistance patterns can help guide rational and safe antimicrobial prescribing in an institution or region.

For intraabdominal infections, blood culture and tissue/pus samples taken in theatre are vital investigations to optimise antimicrobial use and patient outcomes. Newer techniques in microbiology are allowing more rapid and accurate identification of microorganisms. The use of matrix-assisted laser desorption/ionisation – time of flight (MALDI-TOF) can accurately determine the identification of pathogens from cultured material. Other techniques involving nucleic acid amplification techniques and molecular probes for both chromosomal and ribosomal nucleic acids can allow the detection of pathogens where culture techniques fail. These techniques can be used to not only identify the pathogen but also, in some cases, identify genes conferring antimicrobial resistance to allow appropriate antimicrobial therapy.

Prophylactic antimicrobial in surgery

Antimicrobial-prescribing behaviours

In the UK in 2015, the Public Health England issued “Start smart, then focus” guidance focussed on a few key areas for hospital-based practice ( Fig. 6.5 ).

Other areas where antimicrobial use can be minimised include:

• Promoting source control to mitigate the need for antimicrobials, e.g. abscess drainage, appendectomy, biliary stent for cholangitis.

• Using the shortest effective course for treatment. Many common infections have been proven to be safely and effectively treated with short courses of antibiotics ( https://www.bradspellberg.com/shorter-is-better ), including:

  • Lower UTI in women – 3 days

  • Pneumonia – 3 to 5 days

  • Intraabdominal infections – 4 to 8 days

  • Gram-negative bloodstream infections – 7 days

• Using narrow-spectrum antibiotics with minimal effect on gut microbiome and avoiding the 4C antibiotics (coamoxiclav, ciprofloxacin, cephalosporins and clindamycin).

• Following local institutional antimicrobial guidelines.

Surgical antimicrobial stewardship programmes

Behaviour or culture of a clinical team can influence prescribing. Surgical specialties have particular timetables and cultural norms. Antimicrobial stewardship must be embedded into these cultural norms and routines to be effective. Different approaches may be needed between and within different surgical and medical specialties.

Behavioural studies in surgical departments have been undertaken to understand antimicrobial use in surgery. It is not infrequently seen that antimicrobial prescribing is deferred to less experienced members of the team.

Antimicrobial stewardship teams must engage senior decision makers in surgical specialties to engage with guideline development, quality improvement and provide feedback. Influencing change can be difficult. Use of data, particularly data personalised to the prescriber or responsible surgeon, can be very powerful. Comparing data between teams and individuals can lead to discussion of why clinical practice may differ and whether harmonisation of practice is required to reduce variation.

Use of quality improvement methodology can help a clinical team choose a focus for improvement ( Table 6.7 ).

Regular, personalised and face-to-face feedback can help change practice. The antimicrobial stewardship team must understand the factors that drive behaviours in a clinical area including what common indications for antimicrobials are seen in practice, whether they appear in current guidelines and reduce ambiguity or uncertainty in the use of the guideline. This can only be achieved through engagement with all levels and types of healthcare workers in that area. Considering issues of motivation, capability or opportunity of the observed behaviour will aid the antimicrobial stewardship team to identify behaviours to improve practice. Education alone will rarely change behaviour. Developing long-term sustained improvement must consider system design and how best practice can become routine. Training and assessment to facilitate optimal behaviours, seeking microbiology advice in complex cases and proactive patient review by infection specialists in certain settings, such as transplantation or oncology, may all help achieve the best outcomes for patients.

Sepsis definition

International Surviving Sepsis Campaign (SSC) guidelines 2004 promoted early goal-directed therapy. The definition of sepsis was based on the suspicion of an infection along with systemic inflammatory response. The original definition caused considerable concern due to the low specificity of the systemic inflammatory response to identify those who have an infection, those requiring hospitalisation and those requiring antibiotics, never mind urgent antibiotic administration. There remains tension between identifying those patients who will most benefit from early interventions and the harm associated with excessive oxygen delivery, intravenous cannulation, urinary catheter placement, rapid intravenous fluid administration and the overuse of broad spectrum antibiotics.

Other tools have been introduced that may more accurately describe a population of patients who do require more rapid assessment and intervention. This group of patients may also more often require management within a critical care area and have higher mortality.