Cephalosporins are a class of beta-lactam antimicrobials that exert bactericidal effects through disruption of the bacterial cell wall. These broad-spectrum antimicrobials have played a core role in the treatment of severe infections since their launch in the latter half of the 20th century. Early generation cephalosporins provide robust coverage of Gram-positive bacteria, while the newer third- and fourth-generations offer additional Gram-negative coverage, including Pseudomonas for some cephalosporins (such as ceftazidime and cefepime).
In response to the Clostridium difficile infection outbreak in UK hospitals in the mid-2000s, the use of cephalosporins along with quinolones and lincosamides began to decrease across the UK. These therapies were associated with higher acquisition of C. difficile infection; through improved stewardship by local antimicrobial teams, these therapies were gradually replaced within empiric treatment guidelines. Alternative therapies (such as piperacillin/tazobactam, carbapenems and combination therapies) filled the gap left by cephalosporins and coincided with an approximate 50% drop in total cephalosporin use within UK hospitals
This reduction remained constant until 2016, when third-, fourth-, and fifth-generation cephalosporin use began to increase once again. This increase was triggered by acute trusts’ ambitions to avoid use of piperacillin/tazobactam and carbapenem, in line with antimicrobial stewardship targets for Commissioning for Quality and Innovation, and by the introduction of newly licensed cephalosporins.
New agents include: ceftaroline, a fifth-generation cephalosporin that provides methicillin-resistant Staphylococcus aureus coverage; ceftazidime/avibactam (Zavicefta; Pfizer) and ceftolozane/tazobactam (Zerbaxa; Merck), both of which provide extended activity against Gram-negative pathogens; and cefepime (Renapime; Renascience Pharma), a fifth-generation cephalosporin used extensively outside of the UK for past 20 years.
This mix of new therapies and resurgence of older cephalosporins has provided a new challenge for the suppliers, prescribers and administrators of intravenous antimicrobials — risk of product confusion is a very real problem.
At Chelsea and Westminster Hospital NHS Foundation Trust (CWFT), this problem has been realised. From January 2017 to March 2018, 9 out a total 17 reported incidents relating to an incorrect antimicrobial being selected involved a cephalosporin. These include errors across prescribing, administration and supply. CWFT has introduced newer third- and fourth-generation cephalosporins
onto its formulary, and moved older cephalosporins (e.g. cephalexin, ceftriaxone and ceftazidime) back into empiric treatment guidelines. However, busy dispensaries, similar packaging and lack of user familiarity present a challenge to minimising errors in the pharmacy department.
While robotic dispensing can minimise errors, the storage of packed-down vials outside the robot comes with an additional risk — the most notable risk being confusion over the similarity of drug names; cephalosporins are known offenders on the list of ‘look-alike sound-alike’ — or ‘LASA’ — drug names. It is common practice for pharmacies to store medicines in alphabetical order, and therefore mis-selection errors with similar-sounding drug names are predictable, if not, inevitable. These factors combined, indicate that an intervention beyond vigilance is necessary to reduce cephalosporin-related supply errors.
In 2009, the Medicines and Healthcare products Regulatory Agency and the now defunct National Patient Safety Agency set out a labelling system designed to help pharmacy staff reduce mis-selection errors. This system was based on the process of ‘tall-man lettering’, which involves the use of capital letters to highlight the unique portion of the drug name. Although pharmacies were expected to comply with this system, the practice has somewhat diminished. However, it is still widely used in Australia and New Zealand, and all antimicrobial guidelines at CWFT now use tall-man lettering for intravenous cephalosporins. However, electronic prescribing locally defaults to all capitalised text, making this strategy redundant for prescribing.
At the CWFT, cephalosporins are traditionally stored along with all other intravenous preparations in alphabetical order. Loose vials, vials in original packaging and vials packed into plain white boxes are commonly stored together. To reduce user risk of misidentification, we developed a physical divider on the shelf to separate the similar-sounding intravenous cephalosporins. Each section of the shelf containing cephalosporins was labelled with the drug names in Tall Man lettering, and labels now display white lettering on a black background for added effect.
A supplementary label was also added to our dispensing software, which prompts users to check that the correct cephalosporin has been selected at the labelling stage. A department-wide awareness campaign using posters, teaching sessions and feedback on dispensing errors was undertaken to further highlight the risks and changes made to mitigate these.
Since the introduction of this initiative, reported incidents of cephalosporin ‘confusion’ have reduced. Reliance on the newer cephalosporin antimicrobials to treat multi-drug resistant organisms is expected to increase; therefore, we believe other trusts should take action to reduce patient harm and better identify cephalosporins during supply, prescribing and administration.
Sima Purohit, preregistration pharmacist; Chelsea and Westminster Hospital NHS Foundation Trust, London
Stephen Hughes, consultant antimicrobial pharmacist; Chelsea and Westminster Hospital NHS Foundation Trust, London