Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

Objectives: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. Methods: An online survey was sent to all infection consultants in NHS acute hospitals in England. Results: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. Conclusions: The 'subscription-type' model was viewed favourably by infection consultants in England.

Outcomes after hospitalisation with spontaneous bacterial peritonitis over a 13-year period: a retrospective cohort study.

GOALS: Assess outcomes in patients with an index presentation of spontaneous bacterial peritonitis (SBP) over a 13-year period. BACKGROUND: SBP, a bacterial infection of ascites, has a poor prognosis. STUDY: Retrospective cohort study assessing mortality (standardised to 32 months) and prognostic factors in patients with SBP during two periods: period 1 (June 2006-November 2012) and period 2 (December 2012-May 2019). RESULTS: The study included 178 patients who were followed up for 11.6 (29.2) months. Mortality was high, with 12-, 24- and 32-month survival being 32%, 26% and 24%, respectively. Inpatient mortality was 36% with mortality in those surviving hospitalisation being 62%. Serum creatinine at the time of SBP diagnosis was an independent predictor of mortality at 32 months [hazard ratio (HR) 1.002, P = 0.023] and inpatient mortality (HR 1.003, P = 0.035). Positive ascitic fluid culture and ascitic fluid neutrophil count were independent predictors of 32-month (HR 1.679, P = 0.008) and inpatient mortality (HR 1.0001, P = 0.005), respectively. Patients in period 2 had lower ascitic fluid albumin (5.9 ± 3.3 g/L vs. 10.8 ± 5.4 g/L, P < 0.001), higher ascitic fluid neutrophil count (815.0 cells/mm3 vs. 345.0 cells/mm3, P < 0.001) and higher rates of hepatorenal syndrome-acute kidney injury (58 vs. 35%, P = 0.002). Mortality at 32 months and mortality in those surviving hospitalisation were similar at 78 vs. 73%, P = 0.392 and 66 vs. 58%, P = 0.355, for periods 1 and 2, respectively. CONCLUSIONS: Despite more advanced initial presentations, mortality rates have remained similar over the last 13 years. Serum creatinine at the time of SBP diagnosis is an independent predictor of mortality.

The epidemiology of hospital inpatient exposure to SARS-CoV-2: A cohort study.

BACKGROUND: Exposure to SARS-CoV-2 was widespread in hospitals during 2020. The risk of infection after in-hospital exposure has not yet been quantified and effective strategies to prevent it remain unclear. METHODS: All incidences of patient-to-patient exposure to SARS-CoV-2 on non-COVID wards between October and December 2020 at a UK hospital trust were identified. Patient contacts were traced, and data collected on SARS-CoV-2 testing, symptoms, and outcomes. Factors associated with acquiring infection and mortality were investigated. RESULTS: Of 575 patients exposed, 118 (19.5%) tested positive within 14 days of their exposure, with secondary attack rates (SAR) ranging from 0 to 72%. 68.6% (81/118) of secondary cases had not been in the same bay as the index case.For exposed patients, sharing a bay with the index case and having spent longer on the ward with them were associated with acquiring infection (ORs of 3.8, 95% CI: 1.89, 7.74, and 1.08, 95% CI: 1.01, 1.15 respectively). 71% of secondary cases tested positive while asymptomatic and 94.6% had tested negative earlier in their admission. CONCLUSIONS: This is the first study to describe the outcomes of a cohort of patients exposed to COVID-19 in hospital. Exposure to COVID-19 in hospital commonly leads to transmission that is not confined to the index case's bay. This study confirms that asymptomatic testing is important and suggests that an increased frequency of testing may be beneficial. Moreover, we provide factors that can be used to identify the contacts at the greatest risk of acquiring infection.

Long-term outcome and risk factors for late mortality in Gram-negative bacteraemia: a retrospective cohort study.

OBJECTIVES: The long-term outcomes of patients following Gram-negative bacteraemia (GNB) are poorly understood. Here we describe a cohort of patients with GNB over a 2-year period and determine factors associated with late mortality (death between Days 31 and 365 after detection of bacteraemia). METHODS: This was a single-centre, retrospective, observational cohort study of 789 patients with confirmed Escherichia coli, Klebsiella spp. or Pseudomonas aeruginosa bacteraemia with a follow-up of 1 year. Multivariable survival analysis was used to determine risk factors for late mortality in patients who survived the initial 30-day period of infection. RESULTS: Overall, 1-year all-cause mortality was 36.2%, with 18.1% of patients dying within 30 days and 18.1% of patients suffering late mortality. An adverse antimicrobial resistance profile [hazard ratio (HR) = 1.095 per any additional antimicrobial category, 95% confidence interval (CI) 1.018-1.178; P = 0.014] and infection with P. aeruginosa (HR = 2.08, 95% CI 1.11-3.88; P = 0.022) were independent predictors of late mortality. Other significant factors included Charlson comorbidity index and length of hospitalisation after the index blood culture. CONCLUSION: Patients with GNB have a poor long-term prognosis. Risk factors for greater mortality at 1 year include co-morbidity, length of hospitalisation, and infecting organism and its resistance profile.

Impact of antibiotic timing on mortality from Gram-negative bacteraemia in an English district general hospital: the importance of getting it right every time.

OBJECTIVES: There is limited evidence that empirical antimicrobials affect patient-oriented outcomes in Gram-negative bacteraemia. We aimed to establish the impact of effective antibiotics at four consecutive timepoints on 30 day all-cause mortality and length of stay in hospital. METHODS: We performed a multivariable survival analysis on 789 patients with Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa bacteraemias. Antibiotic choices at the time of the blood culture (BC), the time of medical clerking and 24 and 48 h post-BC were reviewed. RESULTS: Patients that received ineffective empirical antibiotics at the time of the BC had higher risk of mortality before 30 days (HR = 1.68, 95% CI = 1.19-2.38, P = 0.004). Mortality was higher if an ineffective antimicrobial was continued by the clerking doctor (HR = 2.73, 95% CI = 1.58-4.73, P < 0.001) or at 24 h from the BC (HR = 1.83, 95% CI = 1.05-3.20, P = 0.033) when compared with patients who received effective therapy throughout. Hospital-onset infections, 'high inoculum' infections and elevated C-reactive protein, lactate and Charlson comorbidity index were independent predictors of mortality. Effective initial antibiotics did not statistically significantly reduce length of stay in hospital (-2.98 days, 95% CI = -6.08-0.11, P = 0.058). The primary reasons for incorrect treatment were in vitro antimicrobial resistance (48.6%), initial misdiagnosis of infection source (22.7%) and non-adherence to hospital guidelines (15.7%). CONCLUSIONS: Consecutive prescribing decisions affect mortality from Gram-negative bacteraemia.