Clinical pharmacy Antimicrobial prophylaxis Lec:2

From the population development of antimicrobial resistant bacteria. There are potential adverse consequences to the administration of antimicrobials for both the individual and the population. For the individual side effects, ranging from antimicrobial associated diarrhoea to life- threatening allergic reactions. From the population development of antimicrobial resistant bacteria.

Antimicrobial prophylaxis should, therefore, only be offered to patients where there is evidence or, in the absence of evidence, expert consensus that the potential benefits of prophylaxis outweigh the risks.

The infection risk associated with a particular surgical procedure and evidence of efficacy should be used to determine whether antimicrobial prophylaxis is to be administered. Not all surgical procedures warrant antimicrobial prophylaxis.

Choice of antimicrobial Once it has been determined that antimicrobial prophylaxis is required, the next step is to select an appropriate agent(s).

The choice of antimicrobial should take into account the following: Likely infecting organisms. Local susceptibility of potential pathogens to antimicrobials. Pharmacokinetics, for example, penetration of antimicrobial to the site(s) in question. Patient allergy to penicillins or other antimicrobials.

Administration time (bolus better than infusion). Drug cost. Carriage of resistant organisms, for example, methicillin- resistant S. aureus (MRSA) Prevalence of Clostridium difficile infection in the hospital.

Timing and duration Timing of antimicrobial administration is one of the most important aspects of prophylaxis regimens. prophylaxis is most effective when given immediately before an operation (within 30 min of induction of anaesthesia), so that antimicrobial activity is present for the duration of the operation and for about 4 h afterwards.

Antimicrobials given too early prior to surgery are associated with prophylaxis failure, presumably because serum and tissue levels are not sustained during the surgical procedure.

Similarly, for each hour antimicrobial administration was delayed after the start of the operation there was an increased rate of wound infection. This suggests bacterial replication, once commenced, cannot be eliminated by antimicrobial regimens designed for prophylaxis.

If bacteria inoculated into a wound can be killed or inhibited by antimicrobials given early, the immune system can kill the remaining organisms. As surgery may be delayed at short notice, sometimes between the time the patient leaves the ward and arrives at the theatre, it is sensible for the administration of antimicrobials to be transferred from ward staff to the operating team when prophylaxis can be given around the time of induction of anaesthesia.

Historically, the only occasion where antimicrobial administration has been delayed to after the incision is Caesarian section, where antimicrobials are given after cross clamping the umbilical cord to prevent drug delivery to the neonate.

When a tourniquet is used during orthopaedic procedures to minimize bleeding, the antimicrobial should be infused before inflating the tourniquet. This ensures adequate tissue levels are achieved at the site of surgery.

Certain practical issues should be considered when selecting an antimicrobial, for example, the requirement for intravenous infusion or safe intravenous bolus administration.

An antimicrobial, which requires to be administered over a long period, for example, vancomycin 1 g over nearly 2 h, is much less likely to be given completely compared to teicoplanin, which is administered as a bolus.

Where single dose prophylactic regimens have been adopted, the need for dosage adjustment in patients with reduced ability to excrete the drug (usually due to renal impairment) becomes unnecessary. This is because it is unlikely that single doses will have significant dose related adverse effects and idiosyncratic reactions are dose independent.

There are some situations in which it is necessary to prescribe additional doses of antibiotics to achieve the aim of adequate tissue levels at the time of wound closure. The additional doses may be needed when there is significant blood loss (>1500 mL) as plasma is effectively diluted by intra-operative transfusions and fluid replacement.

Long operations may also need extra antimicrobial doses during the operation, but additional doses post-operatively do not provide an additional prophylactic benefit.

Antimicrobial administration by oral route tends to suffer from variable absorption, especially in the presence of anaesthetic premedication, and this also makes it unsatisfactory. The intravenous route is the most reliable way of ensuring effective serum levels and is the only route supported by a substantial body of evidence.

After an initial dose of the antimicrobial agent, tissue concentrations reach their peak rapidly, with a subsequent decline over time. The goal of prophylaxis is for the antimicrobial tissue concentration to remain above the minimum inhibitory concentration (MIC) for the specific pathogens at the time of incision and throughout the procedure.

The antimicrobial should be re-administered during prolonged procedures to prevent a period where tissue concentrations are below the MIC. Failure to re-administer antimicrobials appropriately may result in a period during which the wound is vulnerable.

β-Lactam allergy Penicillin and cephalosporin antibiotics have been the cornerstone of antimicrobial prophylaxis to prevent surgical site infections. Patients reported to be allergic to β-lactam antibiotics or other antimicrobials need to be carefully assessed, as alternatives may not be optimal.

Alternatives are often glycopeptides, for example, teicoplanin or vancomycin, which is more expensive, often need to be given by infusion (vancomycin) and can increase selection for resistant bacteria.

The prevalence of penicillin allergy in the general population is unknown. The incidence of self-reported penicillin allergy ranges from 1% to 10%, with the frequency of life- threatening anaphylaxis estimated at 0.01– 0.05% (or 1–5 in 10,000).

Important details of an allergic reaction include signs, symptoms, severity, history of prior reaction, time course of allergic event, temporal proximity to administered drug, route of administration, other medication being taken and adverse events to other medication.

Reactions to penicillins and other β-lactams occur because of allergy to the parent compound or the metabolites. The cross sensitivity between penicillins and cephalosporins is unknown, but has been variably reported to be up to 10%.

Early cephalosporin preparations were contaminated with penicillins probably leading to an over estimate of cross sensitivity. As the generation of the cephalosporin increases, the likelihood of cross sensitivity decreases.

Those with a penicillin allergy showed an increased risk of allergic reaction to a first generation cephalosporin. First generation cephalosporins share a similar side chain to penicillin and amoxicillin. However, cross sensitivity to second and third generation cephalosporins was lower.

The cross- Reactivity to carbapenems and monobactams is very small The cross- Reactivity to carbapenems and monobactams is very small. It is around 1% for imipenem and meropenem, and no cross-reaction has been reported for aztreonam. The current nomenclature for penicillin combinations, for example, co-amoxiclav, can often make it more difficult for staff to recognise penicillin containing antimicrobials.

Topical or local antimicrobial prophylaxis Many surgical procedures involving the use of implants or prostheses now use topical antimicrobials to prevent late surgical site infection. Examples include antimicrobial loaded cement for fixing hip and knee joint replacements into bone.

Gentamicin is the only antimicrobial in commercially available products in the UK. Surgeons do add other antimicrobial agents, especially if replacing an infected prosthesis with choice based on culture and sensitivities.

In vascular surgery, synthetic grafts bonded with or soaked in rifampicin are frequently used, despite evidence showing that there was no decrease in infection rates at 1 month and 2 years.