Chapter 64 Principles of antibiotic use

The intensive care unit (ICU) is always the area of any hospital associated with the greatest use of antibiotics. Much of this high usage is unavoidable, but the clinician working in the ICU must realise that there is an essential consequence of this use. Antibiotic use which should eliminate susceptible organisms promotes (over)growth of other, non-susceptible organisms, especially fungi. As far as bacteria are concerned, antibiotics confer enormous selective advantage to resistant strains, and therefore these strains will congregate where their advantage is greatest, in the ICU. Resistance (and fungal overgrowth) is a direct consequence of usage, and every course of inappropriate antibiotics should be avoided to help reduce the burden of resistance.

Antibiotic stewardship ¹ has been suggested as a new strategy to help limit resistance. This involves selecting an appropriate drug and optimising its dose and duration to cure an infection while minimising toxicity and conditions for selection of resistant bacterial strains. Inadequate doses of even the ‘correct’ antibiotic may lead to survival of initially susceptible organisms.^2,³ For the optimal use of antibiotics not only should antibiotic pharmacokinetics be understood, but there should be clear and rational principles on which each specific antibiotic prescription in the ICU is based. Also, it is probably better to have portions of the ICU population receive different classes of antibiotics at the same time.

Although this chapter will provide basic principles for most of the antibiotic classes commonly used in the ICU, some important antimicrobial agents will not be specifically addressed here, namely macrolides, clindamycin and the antifungal agents.

GENERAL PRINCIPLES ⁴^–⁸

1 All appropriate microbiological specimens, including blood cultures, should be obtained before commencing antibiotic therapy. An immediate Gram-stained report may indicate the appropriate antibiotic to use; otherwise a ‘best-guess’ choice is made, which is dependent on the clinical situation. This important and common clinical phenomenon involves trying to predict the infecting organism(s).

2 Blood cultures should be taken from a venepuncture site, after adequate skin antisepsis, and not from an intravenous or arterial catheter. Two separate sets of 20 ml (for adults) should be taken, the timing of which is less important.⁹ Depending on what system is used, probably 10 ml should be placed into two different blood culture bottles.

3 Once a decision is made to administer antibiotics, they should be administered without delay.

4 The decision for empiric therapy, i.e. cover for the most ‘likely’ organisms causing any specific infection, must include various factors such as the site of the infecting organism (respiratory tract pathogens differ from those of abdominal infections), community versus hospital-associated infection; recent previous antibiotic prescription; ward versus ICU-acquired infection and knowledge of the organisms commonly grown in patients in any specific area. This latter point is where ward/unit surveillance becomes important.^10,¹¹

5 Whilst there should be an attempt to use a narrow-spectrum antibiotic whenever practicable, appropriate therapy, particularly for empirical choice for nosocomial sepsis, mandates initial broad-spectrum antibiotics, even a combination, until culture results are back,¹² at which time de-escalation should be embarked upon (see below). Inappropriate and/or delayed correct antibiotic use in the ICU has been shown to have an impact on morbidity and mortality^12,¹³ (Table 64.1).

6 Monotherapy with a single agent effective against the expected organisms aims to decrease the risk of drug antagonism, reaction or toxicity.^14,¹⁵ Monotherapy often costs less than multiple antibiotic usage.

7 The clinical response to treatment already given should always be considered, when bacteriological results suggest a change in antibiotics.

8 A standard 2-week course of antibiotics is unnecessary and probably harmful. There is a move to use shorter courses for pneumonia ^16,¹⁷ (see Table 64.1).

9 In consultation with infectious disease specialists, additional tests such as antibiotic minimum inhibitory concentration (MIC), antibiotic assay, serum bactericidal activity and synergy tests of antibiotic combinations may be useful in serious infections (e.g. endocarditis and infections in immunocompromised patients). Sensitivity tests should be interpreted carefully. In vitro sensitivity does not equate with clinical effectiveness; in vitro resistance generally predicts clinical ineffectiveness.

10 Consultations with the laboratory staff and infectious diseases/clinical microbiology specialists are always useful and should be mandatory in serious infections (e.g. meningococcal sepsis, meticillin-resistant staphylococci and multiresistant Enterobacteriaceae).

11 The pharmacokinetics and pharmacodynamics (e.g. penetration into relevant tissues) as well as the spectrum of activity of the antibiotic must be considered. Antibiotic pharmacokinetic principles should determine the dosage and frequency of antibiotic regimens (see below).

12 Adequate drug doses should be given. The intravenous route is preferable in critically ill patients, but other routes should be considered when appropriate (e.g. rectal metronidazole ¹⁸).

13 Serum levels of potentially toxic antibiotics should be monitored, especially if hepatic or renal dysfunction is present.

14 Prophylactic use of antibiotics should be limited to certain situations, should cover organisms that can potentially cause infections in that specific group of patients (e.g. organisms causing skin and soft-tissue infections differ from those implicated in intra-abdominal infections) and should be given at the appropriate timing (see below).

15 General signs of infection are signs of systemic inflammation. Although bacterial infection is likely, non-bacterial infection and non-infective causes should also be considered. High procalcitonin and C-reactive protein levels may be discriminatory for infection,¹⁹ as are interleukin-6 levels, although these are difficult to measure.

16 Antibiotic guidelines are only one aspect of infection control.²⁰ Hand-washing and hand hygiene in general are vital and fundamental aspects of infection control.²⁰ Identification and elimination of reservoirs of infection, blocking transmission of infection, barrier nursing, interrupting progression from colonisation to infection and eliminating risk factors such as invasive devices are also important.

Table 64.1 New paradigm of treatment for nosocomial sepsis

Old	New
Start with penicillin	Get it right first time (broad-spectrum)
Cost-efficient low dose	Hit hard up front
Low doses = fewer side-effects	Low dose → resistance
Long courses ≥ 2 weeks	Seldom longer than 7 days