The increasing role of pharmacists in antimicrobial stewardship in English hospitals.

OBJECTIVES: To evaluate the development of pharmacist-led antimicrobial stewardship activities in English hospitals. METHODS: Distribution of an electronic questionnaire to antimicrobial pharmacists or chief pharmacists in National Health Service hospitals in England. RESULTS: Since a previous study, in 2005, overall numbers of specialist antimicrobial pharmacists, and their levels of experience, had increased. Over 95% of hospitals provided empirical usage guidance, antimicrobial formularies and surgical prophylaxis guidelines. Two-thirds of pharmacy departments provided antimicrobial usage reports in terms of defined daily doses at least yearly, and over 80% conducted yearly antimicrobial point prevalence studies. The vast majority of pharmacy departments indicated a willingness to supply data and audit results to a national database for benchmarking purposes. CONCLUSIONS: The increasing role of specialist pharmacists and general pharmacists in antibiotic stewardship in acute care in England has enabled hospitals to deliver on the antibiotic stewardship agenda, although opportunity remains to expand this role further and ensure greater multidisciplinary engagement.

Impact of the Hospital Pharmacy Initiative for promoting prudent use of antibiotics in hospitals in England.

OBJECTIVES: In July 2003, the UK Department of Health announced an allocation of 12 million pounds sterling to hospital pharmacists to improve the monitoring and control of anti-infective use over the ensuing 3 year period (the Hospital Pharmacy Initiative, or HPI). Chief Pharmacists were asked to use this money for developments to promote prudent antibiotic use and monitoring of antimicrobials within their Trusts. This study aimed to evaluate the impact of the HPI funding, which at the time had been in place for nearly 2 years, on pharmacy activities in this area. METHODS: A postal questionnaire was sent to the pharmacy department of each acute hospital Trust in England, aiming to provide a descriptive overview of the activities of hospital pharmacy staff in the field of anti-infectives and to explore the extent to which these activities were made possible by the HPI funding. RESULTS: One hundred and forty-one specialist antimicrobial pharmacy staff were employed in 130 responding Trusts; 89% were pharmacists, 7% pharmacy technicians and the remainder administrative staff. Three-quarters of these staff had been employed due to the funding, resulting in review of antimicrobial prescribing guidelines, antibiotic audit projects and multidisciplinary work with Microbiology/Infectious Diseases staff. Thirteen Trusts gave details of drug acquisition cost savings; over the course of a year, these Trusts saved 1.1 million pounds sterling in total. CONCLUSIONS: The HPI funding has facilitated greater interaction between Pharmacy and Microbiology/Infectious Diseases departments than was previously possible. Significant reductions in antibiotic acquisition costs have been demonstrated, though further work is warranted to fully establish the impact of pharmacy activities on clinical and microbiological outcomes.

Investigation of Smith's quinolone killing mechanisms during the PAE of ciprofloxacin on Escherichia coli.

Quinolone antibacterials interact with the DNA-DNA gyrase complex, but subsequent events that lead to cell death are unresolved. Three distinct mechanisms of quinolone lethality have been identified by Smith and co-workers: Mechanism A, which requires RNA and protein synthesis and cell division for expression; Mechanism B, which remains active when these functions are precluded; and Mechanism C, which is active on non-dividing cells. Exposure to 4x MIC ciprofloxacin (Cip) in nutrient broth (NB) for 3 h reduced the viability of Escherichia coli AB1157 to 0.25%. Addition of rifampicin (Rif) or chloramphenicol (Cm), to inhibit RNA or protein synthesis, respectively, increased survival 70-fold. Treatment of cells with Cip in phosphate-buffered saline (PBS), to inhibit cell division, increased survival 20-fold. No further cell death occurred once the various drug combinations or PBS had been washed out and cells resuspended in drug-free nutrient broth. These latter conditions allow expression of the post-antibiotic effect (PAE). PAE was lengthened in cells exposed to Cip in the presence of Rif or Cm, probably as a result of delay in the initiation of inducible DNA repair.

Flow cytometric investigation of filamentation, membrane patency, and membrane potential in Escherichia coli following ciprofloxacin exposure.

Ninety-eight percent of the cells in a population of Escherichia coli in log-phase growth lost colony-forming ability after being exposed for 3 h to the quinolone antibiotic ciprofloxacin at four times the MIC in nutrient broth, a concentration easily reached in vivo. Flow cytometric analysis, however, demonstrated that only 68% of this bacterial population had lost membrane potential, as judged by the membrane potential-sensitive dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC(4)(3)], and only 30% could no longer exclude the nucleic acid-binding dye propidium iodide (PI), reflecting lost membrane integrity, efflux mechanisms, or both. Subsequent removal of ciprofloxacin and resuspension in nutrient broth resulted in renewed cell division after 2 h, with a calculated postantibiotic effect (PAE) time of 57 min. The proportion of DiBAC- and PI-fluorescent cells in this recovering population remained stable for more than 4 h after antibiotic removal. Eighty percent of cells present at drug removal were filamentous. Their number subsequently decreased with time, and the increase in particle count seen at the end of the PAE resulted from the division of short cells. Exposure to ciprofloxacin in the presence of the protein synthesis inhibitor chloramphenicol increased colony-forming ability to 60% of starting population numbers. In contrast to ciprofloxacin alone, this antibiotic combination resulted in insignificant filamentation and no dye uptake. Subsequent drug removal and resuspension in nutrient broth resulted in the appearance of filaments within 1 h, with 69% of the population forming filaments at 3 h. Dye uptake was also seen, with 20% of the population fluorescing with either dye after 4 h. We were unable to relate dye uptake to the viable count. Cell division resumed 240 min after removal of both drugs, yielding a PAE calculated at 186 min. Inhibition of protein synthesis with chloramphenicol prevented ciprofloxacin-induced changes in bacterial morphology, cell membrane potential, and ability to exclude nucleic acid-binding dye. These changes persisted beyond the end of the classically defined PAE and were not a definite indicator of cell death as defined by loss of colony formation, which related at least in part to filamentation.