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†

Abstract

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.

The Inc FII Plasmid and its Contribution in the Transmission of blaNDM-1 and blaKPC-2 in Klebsiella pneumoniae in Egypt

“…Further, contaminated medical equipment and the hands of health care workers may contribute to sustaining colonization and creating an increased risk of infection [5]. Additionally, antibiotic therapy can suppress normal bacterial flora and lead to an over-growth of multidrug resistant K. pneumoniae [6].…”

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states

“…For example, antibiotic resistance in Enterobacteriaceae, including fluoroquinolone resistance in Escherichia coli was found to be associated with a more severe presentation in urinary tract infections (UTIs) [11,12], while prevalence of fluoroquinolone resistance in E. coli was strongly correlated with rates of septicemia hospitalization in different US states for adults aged over 50y [8]. In a study of cases of E. coli bacteremia in England, urogenital infection had been treated in 310/891 (34.8%) cases in the 4 weeks preceding bacteremia and this sub-population differed very significantly in its antibiotic resistances [13], suggesting treatment failure due to presence of antibiotic resistance prior to the onset of bacteremia. Antibiotic use is one important driver of the prevalence of antibiotic resistance [14][15][16][17][18][19] and thus may contribute to sepsis incidence.…”

2038 – When microbes rule the Earth

“…The spread of antibiotic resistance may allow microbes to rule the Earth in all the wrong ways – by leading to the proliferation of untreatable infectious disease and an ensuing global public health crisis (http://www.who.int/drugresistance/en/). The solutions to this complex and serious problem are multifaceted, and, putting aside the important political, societal and clinical requirements (Hawkey et al ., ), there is a pressing need to understand the ecology and biogeography of multi‐drug resistant bacteria, and the key points at which their spread can be controlled (Berendonk et al ., ). For example, the growing application of anaerobic digestion to transform animal waste into digestate for fertilizer (in addition to biogas for fuel), which is then spread onto agricultural land, has the potential to amplify and release antibiotic‐resistance genes to the wider environment (Youngquist et al ., ).…”

“…However, some of those microbes with which we are in most intimate contact pose the greatest risk, as they are both primed to opportunistically infect us and under high selective pressure to develop multi-drug resistance. This is especially the case for bacteria that colonize our gastrointestinal tract in large numbers, notably the Enterobacteriaceae (Hawkey et al, 2018). The spread of antibiotic resistance may allow microbes to rule the Earth in all the wrong waysby leading to the proliferation of untreatable infectious disease and an ensuing global public health crisis (www.who.int/drugresistance/en/).…”