Antibacterial-resistant gram-negative hospital-acquired infections result in significant morbidity and mortality. In clinical trials, ceftolozane/tazobactam (C/T) has been effective against these infections; however, real-world findings are limited. SPECTRA was a global, retrospective, observational inpatient study of adults treated with C/T for ≥48 hours, conducted between 2016 and 2020. The primary objective was to describe real-world utilisation of C/T: socio-demographic, clinical characteristics, prescribing patterns, clinical outcomes, and healthcare resource utilisation in hospitalized patients treated with C/T. In total, 617 patients from 7 countries met inclusion criteria. Most (82.7%) had ≥1 comorbidity. The most common medical conditions where C/T was used were pneumonia (29.5%), sepsis (20.4%), complicated intra-abdominal infection (15.1%), and complicated urinary tract infection (14.4%). The most common pathogens were Pseudomonas aeruginosa (87.4%) and Escherichia coli (8.2%). Median C/T treatment duration was 11 days. Clinical success occurred in 67.3% of patients (including those with 'unknown' status in the denominator). In a separate analysis that excluded those with 'unknown' status, clinical success ranged from 94.1% in patients with bacteraemia to 58.9% with sepsis. Overall, 18.8% of patients had documented microbiologic response. All-cause in-hospital mortality was 21.2%; infection-related mortality was 7.6%. Median hospital length of stay was 42 days (30 days for those who received early C/T therapy [before pathogen identification] vs. 48 days for definitive therapy [after identification]). These data elucidate real-world utilisation and prescribing patterns of C/T in a diverse patient population with complex medical conditions and various profiles of pathogen resistance between 2016 and 2020.

Objectives: The BSAC Bacteraemia and Respiratory Resistance Surveillance Programmes provided long-term surveillance of antibiotic resistance in key pathogens of bloodstream and both community- and hospital-acquired respiratory infections in the UK and Ireland. This paper details the methodologies used. Data limitations are discussed. Methods: Sentinel laboratories across the UK and Ireland contributed up to a fixed annual quota of isolates of defined bacterial groups. For each Programme, a Central Laboratory confirmed bacterial identifications, measured MICs by the BSAC agar dilution method, investigated mechanisms of resistance and determined serotypes of Streptococcus pneumoniae. Identification methods evolved over time, e.g. with adoption of MALDI-TOF. Classification of susceptibility and resistance follows the 2022 (not contemporaneous) EUCAST guidance. Results: Seventy-nine laboratories contributed 30 716 community respiratory isolates from 1999/2000 to 2018/19; 65 laboratories contributed 13 508 hospital respiratory isolates from 2008/09 to 2018/19; 81 laboratories contributed 56 064 bacteraemia isolates from 2001 to 2019. Although large and teaching hospitals were over-represented, the resistance rates for bacteraemia organisms collected in England mirror more extensive (but less standardized or detailed) national data gathered from laboratories by the UK Health Security Agency and its predecessor organizations, which provided a bespoke data extract. Conclusions: These surveillance Programmes have provided comprehensive and reliable information on antibiotic susceptibility in the UK and Ireland over two decades. Detailed results, showing resistance trends and mechanisms of antibiotic resistance, are presented in five papers in this Supplement.

Background: Antimicrobial resistance is a global health crisis associated with high mortality and economic burden. Patients with renal dysfunction and obesity have increased susceptibility to infections and may experience different real-world outcomes, including clinical success and mortality, but are often under-represented in clinical trials. Ceftolozane/tazobactam (C/T) is an innovative therapy used to treat resistant Gram-negative infections. We aimed to describe real-world clinical outcomes in hospitalized adults treated with C/T across categories of renal function and BMI in the SPECTRA study. Methods: SPECTRA was a multi-national observational study on 617 patients who received C/T for ≥48 h. Outcomes included clinical success, all-cause in-hospital mortality, readmission, and ICU admission and length of stay (LOS), with sub-analysis of patients across BMI and renal function strata. Results: Renal function and weight were reported in 597 and 469 patients, respectively, of which 51.9% had lower creatine clearance (<80 mL/min) and 50.7% were overweight. Clinical success and all-cause in-hospital mortality ranged at 59.1–77.8% and 11.1–29.2% across renal function strata and 64.6–68.6% and 18.6–21.4% across weight subgroups. Across renal function and weight subgroups, 38.9–54.2% and 45.9–53.5% of patients were admitted to ICU. Median ICU LOS was 8–21.5 and 14–20 days, respectively. Readmission (30-day all-cause) occurred in 4.5–11.8% and 8.2–11.9% of patients across renal function and weight strata. Conclusions: Results from this sub-analysis suggest real-world clinical effectiveness of C/T across patients with renal impairment and obesity, highlighting C/T as a component within treatment guidelines for resistant Gram-negative infections.

Background: Ceftolozane/tazobactam (C/T) has demonstrated activity against ESBL-producing Enterobacterales (ESBL-E) and provides a carbapenem-sparing option. Broader use of C/T alongside other carbapenem/inhibitor combinations may expand therapeutic choices and reduce selection pressure for carbapenem resistance, supporting antimicrobial stewardship and limiting the spread of carbapenem-resistant Enterobacterales. Methods: SPECTRA was a multicentre, retrospective real-world study of hospitalized adults (≥18 years) who received ≥48 hours of C/T across seven countries (Australia, Austria, Germany, Italy, Mexico, Spain, UK) from January 2016 to November 2020. Medical-record data were collected for up to 6 months before treatment and 30 days after the final C/T dose (or until death). This sub-analysis describes clinical outcomes and healthcare utilization in patients with laboratory-confirmed ESBL-E (n=39). Results: Thirty-nine ESBL-E patients were included (mean age 59.3 years; 56.4% male); 79.5% had ≥1 comorbidity (mean 2.2 per patient). Common pathogens were Escherichia coli (n=23) and Klebsiella spp (n=12). Investigator-assessed clinical success was 64.9%, microbial eradication was 27.0%, in-hospital mortality was 20.5%, and 30-day readmission was 5.1%. ICU admission during the index hospitalisation occurred in for 38.5% of patients (mean ICU stay 16.0 days). Median treatment duration was 11 days while mean hospital stay after C/T initiation was 13.5 days. Conclusions: In this real-world multi-country cohort, C/T showed clinical effectiveness in ESBL-E infections, with outcomes consistent with the overall SPECTRA population. C/T offers a carbapenem-sparing strategy that broadens treatment options and may help reduce reliance on carbapenems, supporting efforts to limit carbapenem-resistant Enterobacterales. Findings warrant evaluation in larger and comparative studies.

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with substantial morbidity, mortality and therapeutic uncertainty, particularly in critically ill and immunocompromised patients. Imipenem/cilastatin/relebactam (IMI/REL) combines the established carbapenem imipenem with cilastatin, a dehydropeptidase-I inhibitor, and relebactam, a diazabicyclooctane beta-lactamase inhibitor that restores imipenem activity against selected class A and class C beta-lactamase-mediated resistance mechanisms. Methods: A targeted narrative review was undertaken to identify and provide an overview of published observational studies and conference abstracts reporting clinical outcomes with IMI/REL in patients with confirmed or suspected MDR P. aeruginosa infection. Evidence was summarized descriptively, because the available studies were heterogeneous in design, infection site, patient severity, pathogen mix, susceptibility testing and outcome definitions. Results: Real-world IMI/REL data remain limited but are increasingly informative. IMI/REL was commonly used in high-risk patients, including those with pneumonia, bacteremia, intensive care admission, prior antimicrobial exposure, polymicrobial infection or limited alternative treatment options. Reported clinical success or clinical cure was observed in approximately 56–70.2% of patients, although interpretation is limited by non-comparative designs, small patient populations and mixed-pathogen populations. Thirty-day all-cause mortality varied widely, broadly reflecting baseline severity, infection site and salvage-therapy use. Emergence of IMI/REL non-susceptibility was variably reported, but some recent studies report high rates of treatment-emergent resistance; this requires caution and remains an important area for surveillance. Conclusions: IMI/REL appears to be a clinically useful option for susceptible MDR P. aeruginosa infections, particularly in patients with limited alternatives. Available real-world evidence should be interpreted cautiously, because most data derive from retrospective uncontrolled cohorts.

Background: Ceftolozane/tazobactam (C/T) has demonstrated activity against ESBL-producing Enterobacterales (ESBL-E) and provides a carbapenem-sparing option. Broader use of C/T alongside other carbapenem/inhibitor combinations may expand therapeutic choices and reduce selection pressure for carbapenem resistance, supporting antimicrobial stewardship and limiting the spread of carbapenem-resistant Enterobacterales. Methods: SPECTRA was a multicenter, retrospective real-world study of hospitalized adults (≥18 years) who received ≥48 h of C/T across seven countries (Australia, Austria, Germany, Italy, Mexico, Spain, and the UK) from January 2016 to November 2020. Medical-record data were collected for up to 6 months before treatment and 30 days after the final C/T dose (or until death). This sub-analysis describes clinical outcomes and healthcare utilization in patients with laboratory-confirmed ESBL-E (n = 39). Results: Thirty-nine ESBL-E patients were included (mean age 59.3 years; 56.4% male); 79.5% had ≥1 comorbidity (mean 2.2 per patient). Common pathogens were Escherichia coli (n = 23) and Klebsiella spp. (n = 12). Investigator-assessed clinical success was 64.9%, microbial eradication was 27.0%, in-hospital mortality was 20.5%, and 30-day readmission was 5.1%. ICU admission during the index hospitalization occurred for 38.5% of patients (mean ICU stay: 16.0 days). The median treatment duration was 11 days while the mean hospital stay after C/T initiation was 13.5 days. Conclusions: In this real-world multi-country cohort, C/T showed clinical effectiveness in ESBL-E infections, with outcomes consistent with the overall SPECTRA population. C/T offers a carbapenem-sparing strategy that broadens treatment options and may help reduce reliance on carbapenems, supporting efforts to limit carbapenem-resistant Enterobacterales. The findings warrant evaluation in larger and comparative studies.