Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party.

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.

Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013.

OBJECTIVES: The optimal duration of antibiotic treatment in patients with bloodstream infections remains contentious, with concerns regarding both undertreatment and the encouragement of antibiotic resistance. In our ICU we traditionally use short-course antibiotic monotherapy as the mainstay of treatment. We sought to document the impact of this strategy on pathogen type, resistance patterns and patient outcomes. A comparison was made against data collected during a similar exercise in 2000. METHODS: We retrospectively reviewed data on all patients with community-, hospital- and ICU-acquired bacteraemia over a 6 month period (1 December 2012 to 31 May 2013) in a general medical-surgical ICU in a London university hospital. Causative pathogens, resistance patterns, use and duration of monotherapy or combination therapy, breakthrough and relapse rates, and patient outcomes were assessed. RESULTS: The 2013 cohort comprised 113 episodes in 87 patients. Short-course monotherapy (median course 4-5 days) was used in 65.7% of episodes (73.5% in 2000). As with the 2000 cohort, the incidence of antimicrobial resistance, fungaemia, bacteraemia breakthrough and relapse remained low. Of note, there was a decreasing incidence of ICU-acquired MRSA, MDR Gram-negative bacteraemia and fluconazole-resistant candidaemia. Hospital mortality was 32% (45% in 2000). CONCLUSIONS: Our strategy predominantly utilizing short-course antibiotic monotherapy remains effective in achieving good clinical outcomes among patients with bloodstream infections, with low rates of antibiotic resistance and clinical relapse. Prospective trials of short-course monotherapy are warranted to assess clinical efficacy and antimicrobial resistance.