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In most hospitals, ICUs are a focal point of infection, with up to 10% of admissions caused by sepsis, and an even higher incidence of hospital-acquired infection. Early use of appropriate antibiotics is associated with lower mortality, but in most cases conventional culture techniques are too slow to permit narrow-spectrum, tar-geted therapy. The use of broad-spectrum antibiotics means that almost all organisms are treatable, but risks superinfection, adverse events, resistance and higher costs. Guidelines for antibiotic treat-ment of common ICU infections are widely available, but may be influenced by publication bias, and may overemphasize the benefits of newer antibiotics. Rather than reproducing such guid-ance, the aim of this article is to help ICU staff develop their own guidelines, which best suit local flora and resistance patterns.

The role of national/international guidelinesCommon ICU infections are ventilator-associated pneumonia, severe community-acquired pneumonia, intra-abdominal sepsis, vascular catheter-associated bacteraemia and urosepsis. Evidence-based guidelines exist for all of these, and are a useful starting point for developing local policies. They tend to be relatively broad spectrum in their recommendations; and can, at best, be applied to most patients most of the time. Unfortunately, different specialist societies produce strikingly different recommendations, particularly when European and US guidelines are compared. A good example of this is in the treatment of community-acquired pneumonia in adults, where a patient might be treated with cefotaxime plus clarithromycin, ampicillin plus doxycycline, or levofloxacin alone, depending on whether their doctor favours the guidelines of the British Thoracic Society, the American Tho-racic Society or the Infectious Diseases Society of America. These options are probably equally effective, and in many cases, trials of new antibiotics are powered only to demonstrate equivalence with existing agents. Consequently, factors other than efficacy are increasingly important in local policy development.

Modifying guidelines for local useGuidelines are most likely to be successful if they are owned and developed by the ICU staff themselves, rather than being handed down by the microbiologist or Drugs and Therapeutics Committee. This should be a collaborative process, with input from intensiv-ists, microbiologists, infectious diseases physicians, pharmacists and relevant specialists (e.g. chest physicians for pneumonia guidelines). It is inevitably a lengthy process, and needs a dynamic

leader to take it forward. A number of key pieces of local informa-tion should be obtained before starting the review (Figure 1). If these data are available, and can be circulated to interested parties in advance, developing a range of options for common infec-tions should be relatively straightforward. It is important to allow a number of options, particularly to include patients with β-lactam allergy, and renal or hepatic impairment. A choice is also helpful when pharmaceutical companies announce restrictions on supply of antibiotics at short notice, as occurred with meropenem and piperacillin-tazobactam in 2005. Every unit has its own infection control priorities, though MRSA (methicillin-resistant Staphylococ-cus aureus), Clostridium difficile and multi-resistant Acinetobacter affect most UK ICUs to some degree. These should be factored into the decision-making process. For example, a unit with a major C. difficile problem might choose piperacillin-tazobactam over ceftazidime for Pseudomonas infection. A unit in which the main concern was MRSA might try to minimize the use of quinolones. Cost has to be taken into consideration, but only after efficacy and issues of local resistance have been addressed. Guidelines should always be regarded as work in progress, and reviewed rapidly when circumstances change.

Making best use of the microbiology laboratoryGood communication between the ICU and microbiology depart-ments is essential. Advice should be available at all times, and ideally there should be a daily visit by a consultant microbiologist to all critical care areas. A midday visit allows transmission of preliminary results, and discussion of individual cases, informed by current radiology and other results. It also allows the microbiology laboratory time to set up extra antibiotic susceptibility tests and other supplementary investigations as necessary. Microbiology visits should be built into the consultant job plan, and if they happen consistently, most antibiotic treatment decisions can be made at this time.

Screening and surveillanceMany patients admitted to ICU have already had microbiological investigations, on current or previous admissions. These should always be reviewed before empirical treatment of infection and may have a profound effect on the choice of agent, for example if MRSA carriage or recent C. difficile colitis is confirmed. Some units routinely screen for resistant organisms on admission. Other surveillance samples which may be sent, include regular bronchial

Antibiotic prescribing in the ICURichard Cunningham

Richard Cunningham is Consultant Microbiologist at Derriford Hospital,

Plymouth, Devon, UK. He qualified from Trinity College, Dublin, and

trained at Liverpool and Nottingham. His research interests include ICU

microbiology, and rapid diagnostic methods for MRSA and CMV disease.

Preliminary data for review of antibiotic guidelines

• ICU case mix and mean length of stay before ICU admission

• Antimicrobial susceptibility patterns for common infecting

organisms

• Current rates of MRSA (methicillin-resistant Staphylococcus

aureus), vancomycin-resistant enterococci, Clostridium difficile

and any other relevant infection control issues

• Current antibiotic prescribing trends, both on ICU and general

wards

• Existing hospital guidelines, particularly for surgical

prophylaxis

1

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aspirates and measurement of the inflammatory marker, C-reactive protein. This has the advantage of allowing the laboratory to plan its workload, and may allow more targeted antibiotic therapy if colonization precedes overt infection. The cost-effectiveness of this approach is not proven, and other units choose to send samples only when there is a clear clinical indication. The choice of strategy requires discussion between intensivists and their microbiology colleagues, because it will have a profound effect on laboratory workload and antibiotic use. Recent advances in MRSA testing methods make the screening option more attractive. It is possible to screen all critical care admissions with a rapid polymerase chain reaction assay for MRSA, giving a same-day result. This technology is still in its infancy, and cost-effectiveness data are not available.

Antibiotic cyclingAntibiotic cycling involves a deliberate, scheduled removal of one antibiotic and its replacement with another. The replacement anti-biotic is usually of a different class, but with a similar spectrum of activity. Crucially, the cycle must repeat (i.e. return to the original antibiotic choice at some point). It is important that there should not be cross-resistance between the antibiotics, and the usual caveats about allergy and local resistance problems must apply to all agents included in the cycle. Despite theoretical benefits, there are practical barriers to this approach. There is little evidence of benefit from cycling, as opposed to a single change to address a particular resistance issue. In recent reviews, different authors took diametrically opposing views of the same papers, though they agreed that further work was required before cycling could be recommended. It is unlikely to be helpful in routine UK ICU practice, where a wide case mix, pre-existing resistance problems, cost constraints, and a limited range of licensed antibiotic classes make it more of academic than practical interest.

Selective digestive decontamination Selective digestive decontamination has been a controversial infection prevention strategy since its first description in 1984. It involves routine administration of 4 days of parenteral cefotaxime on admission to ICU, together with a mixture of non-absorbed antibiotics applied orally and enterally. A review of the benefits and risks of this approach is beyond the scope of this article; how-ever, it is clear that despite evidence of some benefit in selected patient groups (trauma and burns) it has not been adopted by most intensivists and microbiologists, probably due to concerns over the potential for selecting out resistant bacteria such as MRSA.

FURTHER READINGBrown E M, Nathwani D. Antibiotic cycling or rotation: a systematic

review of the evidence of efficacy. J Antimicrob Chemother 2004; 55: 6–9.

Schultz M J, de Jongel E, Kesecioglu J. Selective decontamination

of the digestive tract reduces mortality in critically ill patients.

Crit Care 2003; 7: 107–10. Also online at http://ccforum.com/

content/7/2/107

Singh N, Yu V L. Rational empiric antibiotic prescription in the ICU.

Chest 2000; 117: 1496–9.

www.anaesthetist.com/icu/infect/ab/abrx.htm Antibiotics in ICU

– a guide for the perplexed. This is a very practical and readable

summary of the issues.