Infectious diseases physicians, clinical microbiologists and hospital pharmacists tend to have a love–hate relationship with the antibiotic ceftriaxone and its stablemate cefotaxime. These potent third-generation cephalosporins have an important place in every Australian hospital formulary, and boast numerous entries in the current edition of Therapeutic guidelines: antibiotic (AG).1 Third-generation cephalosporins (3GCs) are the antibiotics of choice for several life-threatening infections including bacterial meningitis. They are convenient to administer and are among the safest antibiotics available. Yet, these drugs have become the bête noire of hospital epidemiologists. So, what's the problem?

The problem is the increasing burden of resistant bacteria arising from the constant selective pressure exerted by our extensive use of antibiotics, especially very broad-spectrum agents such as 3GCs. Cefotaxime and ceftriaxone are now known to be associated with the emergence of vancomycin-resistant enterococci, resistant gram-negative bacteria, and Clostridium difficile-associated diarrhoea.2-6 They also likely contribute to the emergence of resistant pneumococcus and the ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA).7,8 Third-generation cephalosporins are active against a wide range of gram-positive and gram-negative bacteria and have the added advantage that they penetrate into cerebrospinal fluid and other normally sterile sites, enabling a number of invasive infections to be treated. However, they have only limited activity against anaerobes and staphylococci and are inactive against MRSA. They are also inactive against Pseudomonas, Listeria, and enterococci — all causes of potentially life-threatening infections in immunocompromised patients.

In Australia, we have an antibiotic guidelines handbook that is clear, concise, accurate, extensively peer-reviewed, regularly updated, and, from my own experience, extremely useful! Yet, in this issue of the Journal, Robertson and colleagues (page 524)9 have identified a widespread prescribing problem — and one that probably extends far beyond 3GCs. In a study involving most Victorian hospitals, they found extensive inappropriate use of cefotaxime and ceftriaxone. Three areas of prescribing deserve particular mention. About half of all use of these antibiotics involved empiric treatment of respiratory tract infections, and over three-quarters of these courses were not in concordance with the then current edition of AG. This is despite the fact that simpler regimens are likely to be at least as effective.10 The two other key problem areas found by the authors were inappropriate use for surgical prophylaxis and for treatment of skin and soft tissue infections. As Robertson and colleagues state, improving concordance in surgical prophylaxis should be readily amenable to intervention by withdrawing 3GCs from operating theatres. However, improving concordance in empiric therapy of respiratory and skin and soft tissue infections will require a truly concerted educational effort.

A perusal of the current edition of AG1 reveals that 3GCs don't rate a mention in the first-line regimens for empiric treatment of many common infections in non-penicillin-allergic patients. They are not included in any of the first-line regimens for community-acquired or hospital-acquired pneumonia, and not included at all for the treatment of cellulitis or erysipelas or postoperative wound infections. They have virtually no role in surgical wound infection prophylaxis. Clearly, there is discordance between guidelines and practice. After 11 editions of AG in Australia, what more can be done to curb the high rate of inappropriate use of important antibiotics?

The United States Centers for Disease Control and Prevention recently highlighted 12 clinicians' "action steps" for preventing antimicrobial resistance in hospitals (Box).11 Improved implementation of clinical guidelines is implicit in these steps. Although the steps highlight inter alia the role of vancomycin in the emergence of antimicrobial resistance, similar recommendations could be applied to 3GCs. Implementation of guidelines must be multifaceted and preferably supported by published evidence.12 In Australia, we must first ensure there is comprehensive and practical access to endorsed guidelines among Australian doctors. No recent surveys of access to AG have been conducted, but they appear to be widely available — almost 20 000 copies of the current edition have been sold to date (Mary Hemming, Chief Executive Officer, Therapeutic Guidelines Limited, personal communication). The Australian medicines handbook13 is also a valuable emerging resource now in its third edition. Given that many of the concordance issues highlighted by Robertson and colleagues also apply to other areas of prescribing, universal access to a range of appropriate prescribing guidelines is an essential and logical complement to the training and continuing education of all doctors in Australia. At the very least, 24-hour paper and electronic access to appropriate guidelines should be available to every public hospital doctor and medical student. Personal digital assistants are also emerging as a major practical platform that should expand access to clinical reference programs.14

Improved and adequate access to clinical guidelines is, however, only the first step to control of inappropriate use of 3GCs. Adherence to guidelines requires the support and endorsement of opinion leaders and medical educators and, in particular, obliges senior clinicians to set an example through sensible prescribing. Pharmacists should be given a greater educational role in both hospital and community practice through academic detailing, surveillance of prescribing patterns, feedback to doctors, participation in clinical decision making, and provision of relevant guidelines to specific clinical groups. Most hospital drug committees attempt to adapt generic guidelines to local conditions, which generally involves imposing restrictions on the prescribing of 3GCs and other broad-spectrum antibiotics. Their efforts are supported by the many studies that attest to reductions in the incidence of resistant bacteria and C. difficile following institution of programs to reduce use of 3GCs.8,15,16 Drug committees also have an important role in monitoring the influence of pharmaceutical industry promotions on local prescribing practice.

Recent advances in medical informatics herald exciting new approaches to prescribing in Australia over the forthcoming decade. A range of opportunities is emerging for computerised integration of prescribing guidelines with clinical decision making. Although the main aims are to prevent errors, improve quality of care and reduce costs,17 there is obvious opportunity for benefit at the community level by reducing the burden of resistant bacteria through appropriate prescribing of antibiotics. Many general practitioners in Australia are already using integrated electronic prescribing programs such as Medical Director (Healthcare Portal) and pathology reports have become integrated with prescribing guidelines. The major challenge now is applying computerised prescribing decision-support programs for real-time guideline implementation in hospital wards and emergency departments.18,19 Their application to desktop computers is certainly feasible. Their application to personal digital assistants as a real-time, remote, wide-area data-access and decision-support device is an evolving challenge that will require a major change in the way we approach drug prescribing in hospitals. The report by Robertson and colleagues is not only a timely reminder of the importance of regular evaluation of drug use, but should also inspire us to seek and embrace opportunities to improve antibiotic prescribing in this country.