Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Postdischarge Unscheduled Care Burden After Lower Limb Arthroplasty.

BACKGROUND: In contrast to postdischarge arthroplasty readmission rates, the unscheduled reattendance burden to primary care is under-reported. Understanding reasons for reattendance would allow for implementation of strategies to reduce this burden. The present study aims to quantify the out-of-hours (OOH) general practitioner and emergency department (ED) service reattendance burden and readmission rate after primary total hip arthroplasty and total knee arthroplasty, with estimation of the associated costs. METHODS: This is a prospective consecutive cohort study. A prospective audit of all total hip arthroplasty and total knee arthroplasty patients in 2016 in a single high-volume UK arthroplasty unit was performed. Incidence and reasons for reattendance to OOH and ED service, as well as readmission rates, at both 30 and 90 days following discharge are reported. A multivariate analysis was performed to determine patient characteristics, which results in increased reattendance and readmission rates. RESULTS: A total of 2351 procedures resulted in 374 attendances of OOH service and 665 to ED with a total estimated cost of £190,000 within 90 days. The readmission rate was 6.8%. Risk factors for reattendance and readmission were increasing age and a prolonged length of stay. The use of a 5-day postdischarge phone call and a dedicated Arthroplasty Care Practitioner favors reduced reattendances but not the readmission rate, with the additional benefit of being cost-effective. CONCLUSION: The postdischarge arthroplasty reattendance burden is associated with significant costs, and strategies to reduce this should be developed. Further research is required to assess the effectiveness and cost-effectiveness of multicomponent strategies to reduce reattendance operating at scale.

Meeting the societal need for new antibiotics: the challenges for the pharmaceutical industry.

The rise of antibiotic resistance is leading to clinicians being increasingly faced with clinical failure due to the lack of effective and safe treatment options. New antibiotics are needed now for current multi-drug resistant infections but also in preparation for emerging and anticipated threats. There are significant challenges for the pharmaceutical industry to discover and develop new antibiotics including a business model that balances reasonable reimbursement with appropriate use. This summary reviews the key challenges and collaborative interventions that may contribute to addressing a societal problem.

The consequences of early discharge after hip arthroplasty for patient outcomes and health care costs: comparison of three centres with differing durations of stay.

OBJECTIVE: To compare outcomes from hip arthroplasty between a surgical unit with a rapid discharge policy and two comparison units to test the hypothesis that the centre with rapid discharge has outcomes that are not inferior to the comparison sites. DESIGN: Prospective cohort study. SUBJECTS: Consecutive consenting patients receiving primary hip arthroplasty during 12 months beginning July 2006 in three UK National Health Service surgical units. One has shortened postoperative stay to median three days; one was a new treatment centre with median stay of five days; the third was a traditional unit with median stay of six days (N = 316, 119, 87, respectively). METHODS: Patients were assessed preoperatively and six weeks postoperatively. The primary indicator of function was the Oxford Hip Score. Additional secondary measures included further self-report indicators of function and quality of life and health service costs. RESULTS: Patient outcome in the unit with rapid discharge was not impaired by comparison with the other sites on any measure: Oxford Hip Score decreased from 49 to 27 in the short-stay unit, from 40 to 30 in the treatment centre and from 43 to 32 in the traditional unit. Cost of arthroplasty was least in the short-stay unit, although there was potential for cost savings in each. CONCLUSION: Short postoperative stay after hip arthroplasty can be achieved without intensive patient preparation or post-discharge care and without compromising short-term patient outcome or increasing health care costs. Longer term follow-up is needed.