Background:Antimicrobial resistance poses a significant threat to global health, with Gram-negative pathogens contributing to morbidity, mortality and healthcare costs. While ceftolozane/tazobactam provides an effective treatment option against these pathogens, real-world data on healthcare resource use associated with ceftolozane/tazobactam, especially outside the USA, remain limited. Materials and methods:This retrospective, multinational observational study includes 617 adult inpatients from Australia, Austria, Germany, Italy, Mexico, Spain and the UK who received ≥48 hours of ceftolozane/tazobactam. The outcomes included 30-day all-cause and infection-related readmission rates, hospital length of stay and post-ceftolozane/tazobactam length of stay. Subgroup analyses were conducted by rank of ceftolozane/tazobactam initiation, ICU admission and cystic fibrosis status. Results:The overall 30-day all-cause readmission rate was 10.2%. The infection-related readmission rate was 4.9%. The median hospital length of stay was 42 days (IQR 22-71), and median post-ceftolozane/tazobactam length of stay was 6 days (IQR 1-25). Among ICU patients (n = 298), the 30-day all-cause readmission rate was 3.4% and median length of stay was 59 days. In cystic fibrosis patients (n = 64), the 30-day all-cause readmission rate was 10.9% and the median length of stay was 31.5 days (IQR 16-48.5). Conclusions:This is the largest multinational, real-world dataset on healthcare resource use associated with ceftolozane/tazobactam outside the USA. These descriptive findings show differences in readmission rates and length of stay across rank-of-initiation groups; however, no causal relationships can be inferred from these data. The results are hypothesis-generating for future adjusted and economic analyses. Further research is warranted for economic evaluations and to optimize the timing of ceftolozane/tazobactam initiation.

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.

BACKGROUND:This research was motivated by the widespread use of oral antivirals during the Covid-19 pandemic and the remaining uncertainty regarding their effects on viral kinetics, which have rarely been studied in real-world population cohorts of this size. METHODS:We analysed 291,340 SARS-CoV-2 cycle threshold (CT) values from 113,399 non-hospitalized adult patients in Vienna (01/2022-05/2023), including 30,451 from 12,166 nirmatrelvir-ritonavir recipients, 27,959 from 10,752 molnupiravir recipients, and 232,930 from 90,481 untreated controls. RESULTS:Both antivirals initially caused a rapid increase in mean CT values. After completion of the 5-day treatment course, CT values declined in both antiviral groups, which was not observed in untreated individuals. CONCLUSIONS:These findings provide population-level evidence on post-treatment viral kinetics of oral antivirals during the Omicron wave.

Cutaneous and mucosal/mucocutaneous Leishmania infections may present with very different clinical signs depending on the involved species, the site of infection and the immune status of the host. Leishmania species are intracellular protozoan pathogens transmitted by phlebotomine sand flies, of which over 20 species infecting humans have been described. Leishmania infections are rather common, with an estimated number of one million new cases per year worldwide. The countries with the highest incidence of cutaneous leishmaniasis cases are Afghanistan, Algeria, Brazil, Colombia, Iraq, Libya, Pakistan, Peru, Syria, and Tunisia, while most mucocutaneous cases occur in Bolivia, Brazil, Ethiopia, and Peru. The disease is also endemic in all Southern European countries, with approximately 700 autochthonous human cases reported each year and many more asymptomatic infections. Central Europe is considered non-endemic for the disease; however, epidemiological patterns are affected by travel habits, migration, globalization, and climate change. This review focuses on the diagnostic procedures and treatment options for cutaneous and mucocutaneous Leishmania infections.

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: Patients with cystic fibrosis (CF) experience recurrent infections requiring repeated antimicrobial therapy, leading to high rates of multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) and contributing substantially to disease-related mortality. Ceftolozane/tazobactam (C/T) is an innovative therapy used to treat resistant Gram-negative infections, with enhanced activity against P. aeruginosa infections. Methods: The Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA) was a multicenter, retrospective real-world study of hospitalized adults who received ≥48 h of C/T across seven countries. Medical record data were collected for up to 6 months before treatment and 30 days after the final C/T dose (or death). This subgroup analysis describes clinical outcomes and healthcare resource utilization (HCRU) among hospitalized adults with CF who received C/T for an index infection. Results: Of 64 patients with CF, 53.1% had MDR P. aeruginosa. Clinical success was achieved in 78.1% of patients, with highest and lowest success rates in patients treated with C/T as second (100%) and sixth or later (40.0%) treatment. Microbial eradication was reported in 10.9% of patients. In-hospital mortality occurred in 14.1% of patients, with the lowest percentage in patients treated with C/T as first or second line treatment (0.0%) and the highest in patients treated with C/T sixth or later (40.0%). Median LOS was 31.5 days. Readmission (30-day all-cause) occurred in 10.9% of patients. Conclusions: In this SPECTRA subgroup analysis, C/T was associated with favorable real-world clinical outcomes among hospitalized adults with CF treated for an index infection. Interpretation is limited by the retrospective design, heterogeneous infection indications/sites, and limited interpretability of microbiologic endpoints in CF.

Background: AMR is a public health concern which leads to high global morbidity and mortality. Immunocompromised patients, who are more susceptible to contracting potentially life-threatening infections, are faced with reduced treatment options due to emerging AMR. Ceftolozane/tazobactam is a novel β-lactam/β-lactamase inhibitor which displays effectiveness against resistant Gram-negative infections. Methods: SPECTRA was a multinational, observational study conducted in seven countries including 617 patients who received ≥48 h of ceftolozane/tazobactam. Medical-record data were collected up to 6 months before treatment and 30 days after the final dose or until death. This analysis describes clinical outcomes and healthcare resource use in patients with sepsis or who were immunocompromised, specifically in patients with hematologic malignancy with and without solid tumor, febrile neutropenia, and solid organ transplant patients. Results: Clinical success ranged from 50.0% in patients with hematologic malignancy and solid tumor to 69.4% in 38 patients with febrile neutropenia. All-cause in-hospital mortality was 23.1-42.9%, with the lowest rates in patients with solid organ transplant. ICU admission was 46.4-68.2% across subpopulations (excluding febrile neutropenia) with the lowest rates in patients with hematologic malignancy. ICU length of stay was lowest within transplant patients (9 days) and highest within the hematologic malignancy and solid tumor population (32 days). Conclusions: The results from this sub analysis of SPECTRA showed that ceftolozane/tazobactam was associated with clinical success in the selected immunocompromised and sepsis patient populations and may lead to reduced morbidity, mortality, and healthcare-resource use. Further research is required to standardize treatment protocols and improve patient outcomes.

A sub-analysis of SPECTRA (Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis) aimed to analyze healthcare resource utilization among 298 critical care patients stratified by the rank of chemotherapy or targeted therapy (C/T) initiation, focusing on 30-day all-cause readmissions, infection-related readmissions, prolonged hospital stays, and median length of hospital stays post-C/T initiation (n=298). SPECTRA was a multicenter, observational study in patients (≥18 years of age) treated with ≥48 h of C/T in a hospital setting. For HCRU, data were categorized by the rank of C/T initiation: First Rank (N=74), Second Rank (N=70), Third Rank (N=57), Fourth Rank (N=43), Fifth Rank (N=26), and Sixth or more Rank (N=28). The study examined 30-day all-cause readmission rates, 30-day infection-related readmission rates, the number of patients remaining hospitalized 30 days post-C/T initiation, and median hospital length of stay overall and post-C/T initiation for patients discharged within 30 days. 30-day All-Cause Readmission Rate was 3.4% (variations:1.4% to 4.7% across ranks). 30-day infection-related readmission rate averaged 1.7% overall, (variations: 0% to 3.8%). Patients remaining hospitalized 30 Days after C/T initiation (n=64; 21.5%) were predominantly in the first four ranks. Median hospital length of stay (LOS) was 59.0 days (52.0-72.0). Median Post-C/T LOS for patients discharged within 30 Days was 8.0 days overall, with durations ranging from 4.0 to 12.0 days. In conclusion, the examination of HCRU among critical care patients in the SPECTRA study reveals variations in readmission rates and hospital lengths of stay by the rank of C/T initiation. Further research is warranted to explore factors influencing these variations in HCRU, by novel antibiotics such as C/T. Future research may benefit antimicrobial stewardship and resource management in critical care environments. Emre Yucel, PhD, Merck & Co., Ltd: Stocks/Bonds (Public Company) Jessica Levy, n/a, Merck & Co., Ltd: Stocks/Bonds (Public Company)

Objectives: The real-world effectiveness of the oral antivirals nirmatrelvir-ritonavir and molnupiravir against the SARS-CoV-2 Omicron variant remains uncertain. We aimed to estimate their effectiveness in non-hospitalized adults with COVID-19. Methods: This retrospective cohort study used data from the Municipal Department for Public Health Services of Vienna, Austria, to identify non-hospitalized adults with confirmed SARS-CoV-2 infection between January 2022 and May 2023. Nirmatrelvir-ritonavir users were compared with untreated controls and molnupiravir users with untreated controls by calculating adjusted risk differences (aRDs) using a covariate-adjusted logistic regression model with inverse probability weighting. Outcomes were hospitalization and all-cause death within 28 days. Results: We identified 113 399 eligible cases (90 481 untreated controls, 12 166 nirmatrelvir-ritonavir users, and 10 752 molnupiravir users). Over 96% of the patients were immunized by previous infection or vaccination. In the nirmatrelvir-ritonavir analysis, the estimated risk of hospitalization was 0.57% (95% CI, 0.35-0.78) in nirmatrelvir-ritonavir users and 1.09% (95% CI, 0.86-1.32) in untreated controls (aRD, -0.53%; 95% CI, -0.77 to -0.28). The estimated risk of death was 0.0% (95% CI, 0.0-0.0) in nirmatrelvir-ritonavir users and 0.13% (95% CI, 0.08-0.18) in untreated controls (aRD, -0.13%, 95% CI, -0.18 to -0.08). The number needed to treat to prevent hospitalization and death was 190 (95% CI, 130 -356) and 792 (95% CI, 571-1289), respectively. These statistically significant aRDs were restricted to the subgroup of patients >= 60 years. In the molnupiravir analysis, the estimated risk of hospitalization was 1.36% (95% CI, 0.95-1.77) in molnupiravir users and 1.16% (95% CI, 0.93-1.39) in untreated controls (aRD, 0.2%; 95% CI, -0.08 to 0.49). The estimated risk of death was 0.12% (95% CI, 0.01-0.23) in molnupiravir users and 0.14% (95% CI, 0.06-0.21) in untreated controls (aRD, -0.01%; 95% CI, -0.08 to -0.06). Discussion: Among outpatients aged >= 60 years with COVID-19 in an Omicron-dominated era, treatment with nirmatrelvir-ritonavir was associated with a lower risk of hospitalization and all-cause death within 28 days, albeit with wide CIs and high numbers needed to treat. This finding was not observed molnupiravir users and younger nirmatrelvir-ritonavir users. Anselm Jorda, Clin Microbiol Infect 2025;31:451 (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Abstract Background This sub-analysis of the SPECTRA (Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam [C/T] Real-world Analysis) study aimed to describe the clinical characteristics, treatment patterns, and outcomes of hospitalized pneumonia patients treated with ceftolozane/tazobactam (C/T).Table 1.Patient characteristics and Microbiology2 Immunocompromised defined as: ‘Immunocompromised present’ [raw item] or ‘Hematologic Malignancy present’ or ‘Solid Tumor present’ or ‘Transplant=Yes’. Methods SPECTRA was a multicenter observational study conducted in 7 countries. It included adult patients (age≥18yrs) who received ≥48-hours C/T treatment (n=617). Retrospective data were extracted from medical records covering a 6-month period prior to the index date, up to 30 days after the last dose of C/T or until death. Descriptive statistics were used to analyze clinical success, all-cause in-hospital mortality (ACHM), intensive care unit (ICU) admission, length of stay (LOS) in the subcategory of pneumonia (n=182).Table 2.Outcomes with Ceftolozane/tazobactam and Treatment duration (days) (Treatment interruptions not included)*Other conditions: Bile duct anostomic leakage, Brain-vascular hemorrhagic accident, CMV infection, Encephalic Death, Hemorrhage, Invasive fungal infection, Necrotizing pancreatitis, Post operative complication, Renal amyloidosis, Spontaneous rupture of the spleen, Septic shock, Hemodynamic dysfunction, Kidney failure, Stable angina grade I-II CCS, Probable Clostridium difficile colitis, Progression of AML, Refractory Hypoxemia, Refractory hematologic malignancy, Subarachnoid Hemorrhage, Solid tumor, Tracheobronchitis Results The median duration of C/T treatment was 11.0 days, median time from index hospitalization admission to C/T initiation was 19.0 days, and from the first microbiological sample to C/T initiation 6.0 days. All-cause in-hospital mortality was 32.4% (n=59), with a median time from the index to death of 28.0 days. The causes of death included sepsis (38.9%) and pneumonia (18.6%) and 67% (n=122) patients were admitted to the ICU during the index hospitalization. Pseudomonas aeruginosa (PSA) was the most commonly isolated pathogen (88% of patients), with MDR PsA present in 68.4% (n=80) of pneumonia patients. Conclusion In hospitalized patients with pneumonia treated with C/T in a real-world setting, clinical characteristics, treatment patterns, and outcomes provide insights into the use and effectiveness of C/T. Disclosures Emre Yucel, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) David Paterson, bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Grant/Research Support|Shionogi: Honoraria Florian Thalhammer, MD, MSD: Advisor/Consultant Stefan Kluge, Prof. Dr. med., Merck & Co: Advisor/Consultant|Merck & Co: Board Member Mike Allen, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Brune Akrich, MD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Yanbing Zhou, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company)

Aim: The aim of this study was to investigate the diagnostic performance of a novel rapid multiplex polymerase chain reaction (mPCR) in adults with suspected acute native joint infection. Methods: This retrospective single-centre study included 143 patients with suspected acute native joint infection from February 2023 to May 2024. A septic arthritis was classified based on institutional criteria. The agreement between mPCR and conventional culture of synovial fluid (SF) was assessed by calculating the Cohen's κ coefficient. The diagnostic performance of mPCR was calculated, and the area under the curve (AUC) was compared with conventional culture of synovial fluid by using the z test. Results: When considering only microorganisms targeted by mPCR, this method detected 13 novel microorganisms in 13 cases compared to conventional culture, resulting in an overall agreement of 91 %, a positive agreement of 100 %, a negative agreement of 88 %, and a Cohen's κ coefficient of 0.780. Of these 13 cases, 9 were classified as septic, with 6 (n=6/9, 67 %) on antibiotics prior to aspiration. When considering all microorganisms (including off-panel microorganisms), the overall percentage agreement between mPCR and conventional culture was 89 %, with a Cohen's κ coefficient of 0.735, indicating substantial agreement. Sensitivity, specificity, PPV, NPV, LR+, LR−, accuracy, and AUC of mPCR were 45 %, 89 %, 90 %, 44 %, 4.21, 0.62, 59 %, and 0.671, and those of conventional culture were 40 %, 100 %, 100 %, 45 %, 0.60, 59 %, and 0.698. No difference in performance was observed between both methods (p=0.183). The combination of both techniques showed a sensitivity, specificity, PPV, NPV, LR+, LR−, accuracy, and AUC of 48 %, 89 %, 90 %, 46 %, 4.5, 0.58, 62 %, and 0.686. Conclusion: Given its comparable diagnostic performance and faster turnaround time relative to conventional synovial fluid culture, this novel mPCR can be recommended as a valuable adjunct in the diagnosis of septic arthritis in adults, particularly in patients with prior antimicrobial treatment.

OBJECTIVES:In hospital settings, both pre-existing antibiotic-resistant Gram-negative (GN) bacteria and those that develop resistance during treatment pose significant challenges, often contributing to significant morbidity and mortality. This study focuses on chronic pulmonary disease (CPD) and respiratory-related infections (RRI), including pneumonia, from SPECTRA study. Understanding the real-world clinical use and outcomes for patients treated with ceftolozane/tazobactam (C/T) is essential. METHODS:The multi-national SPECTRA study utilised inpatient chart reviews to describe real-world practice and collect outcome data in hospitalised patients treated with C/T. This analysis focuses on secondary data from SPECTRA cohorts of CPD and RRI patients (the most common conditions comprising RRI included pneumonia and exacerbation of chronic respiratory infection [ECRI]). RESULTS:Between January 2016 and October 2020, 180 patients with CPD, 275 with RRI, 182 with pneumonia, and 91 with ECRI who received C/T for ≥48 h were included. The mean (standard deviation [SD]) age was 57.5 (18.7) years, 55.8 (18.2) years, 57.8 (17.4) years, and 51.8 (19.1) years in CPD, RRI, pneumonia, and ECRI patients, respectively. Pseudomonas aeruginosa was the most frequent pathogen, identified (91.5%, 91.8%, 88.0%, and 97.0% CPD, RRI, pneumonia, and ECRI patients, respectively), with MDR strains in 76.9%, 74.7%, 68.4%, and 80.3% CPD, RRI, pneumonia, and ECRI patients, respectively. Clinical success was achieved in 69.4%, 66.2%, 59.9%, 79.1% of CPD, RRI, pneumonia, and ECRI patients, respectively. CONCLUSIONS:This SPECTRA subgroup analysis demonstrates significant real-world utilisation of C/T in treating patients with CPD and RRI, aligning with previous controlled studies.

To assess COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19. This prospective cohort study enrolled 112 consecutive individuals who recovered from mild-to-moderate COVID-19 and underwent an MRI of the brain between September 2020 and March 2022. MR exams were consistently obtained on a clinical 3T MR scanner in all study participants and 50 age-matched matched controls. The following clinical neuroradiological MR imaging findings were analyzed: post- and acute ischemic lesions, cortical signal alterations, microbleeds, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and vascular abnormalities. Additionally, we manually quantified white matter lesion loads and the number of perivascular spaces and performed an automated brain volumetric analysis. In 112 consecutive individuals the mean age was 45 years, female: male = 70:42, mean days at MRI after SARS CoV-2 infection: 228 (sd: 140), and hospitalized: non-hospitalized ratio = 30:82. Using general linear regression models, adjusting for age and gender, the frequency of white matter hyperintensities was not significantly different between subjects who recovered from COVID-19 and matched controls: 9.8 (sd: 17.3) vs. 7.6 (sd: 12.7), p = 0.590. Similarly, the number of enlarged perivascular spaces was not significantly different between the two groups: 62.7 (sd: 43.5) vs. 61.3 (sd: 47.2), p = 0.902. A subgroup analysis between those who were hospitalized in the course of the disease, in which no one required intensive care, and those who remained outpatients, also did not reveal any differences in MRI measures. We did not find evidence for perfusion-/diffusion abnormalities, (micro-)hemorrhages, or cortical abnormalities. In the present cohort, there was currently no evidence of COVID-19-related morphological brain changes in individuals who recovered from mild-to-moderate COVID-19.

Abstract Background This sub-group analysis of the Study of Prescribing Patterns and Effectiveness of Ceftolozane/Tazobactam(C/T) Real-world Analysis (SPECTRA) described treatment patterns and outcomes in hospitalized patients with Febrile Neutropenia (FN).Table 1.Treatment patterns of Febrile Neutropenia by C/T and C/T Treatment duration and All-Cause In-Hospital Mortality (ACHM)Abbreviations: CRI= Chronic Respiratory Infection cIAI= Complicated Intra-abdominal Infection cUTI= Complicated Urinary Tract Infection (1) For patients aged 90 or older the HCP was asked not to enter the exact age and to check a specific box. Therefore, patients aged 90 or older are included in 'Missing' and are not taken into account in the calculation of mean, median, etc. (2) Several indications may have been reported for the same patient. (3) A patient is counted once for each single indication or combination of indications. Methods SPECTRA was a multicenter, observational study, in hospitalized adult patients treated with C/T for ≥48 hours in 7 countries (n=617). Medical records were extracted, covering 6 months prior to the index date, up to 30 days after the last dose of C/T or until death. Descriptive statistics were reported here on treatment patterns, all-cause in-hospital mortality (ACHM), clinical success and microbiologic response in cases of Febrile Neutropenia (FN, n=38).Table 2.Clinical Success, Microbiologic Response, and Duration of GN antibacterial therapy (days) between Neutropenic and non-Neutropenic patients1Analysis includes only those with known status for clinical success, and only those with known status for microbiological response. Responses of 'Unknown' are considered as missing data. Microbiological response was defined as negative culture result at site of index infection with same organism post C/T administration. Results The median duration of C/T treatment was 8 days, median time from index hospitalization admission to C/T initiation was 18 days, and from the first microbiological sample to C/T initiation 3.5 days (Table 1). ACHM was 9.2% (n=12). Clinical success was 69.4% (n=25) (Table 2). 63% of the patients (n=24) received suboptimal doses for treatment. MDR Pseudomonas aeruginosa and, ESBL-producing Enterobacterales were isolated in 15 and 4 patients, respectively. One had a clinical diagnosis of both pneumonia and sepsis, 2 patients with pneumonia, 4 with respiratory related infections, 1 with skin infection, 3 with sepsis, 1 with cIAI, and 2 with cUTI, in addition to FN. Microbiologic response was achieved for 30.6% of the patients, who received a median of 17 days of GN antibacterial therapy.Table 3Appropriate* Dose of C/T by Indication for Index Event*If the dose received was different (lower or higher) from the appropriate dose as defined, then the patient was considered as not having received the appropriate dose. If the dose received was different (lower or higher) from the appropriate dose on the first day but was then adjusted to the appropriate dose, then the patient was considered as having received the appropriate dose. For patients having both respiratory and non-respiratory infection, the appropriate dose for respiratory infection (=the highest dose) was considered as the appropriate dose for the patient. Conclusion These findings demonstrate potential new findings for the treatment of febrile neutropenia. However, further research is needed to explore its full potential and optimize dosing strategies for improved outcomes. Disclosures Yanbing Zhou, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) David Paterson, bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Grant/Research Support|Shionogi: Honoraria Florian Thalhammer, MD, MSD: Advisor/Consultant Stefan Kluge, Prof. Dr. med., Merck & Co: Advisor/Consultant|Merck & Co: Board Member Mike Allen, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Brune Akrich, MD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Emre Yucel, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company)

Cryptococcal sepsis has primarily been described in patients suffering from advanced HIV associated acquired immunodeficiency syndrome (AIDS) and liver cirrhosis. The most reported clinical manifestation of disseminated cryptococcus sepsis is meningitis. In this patient constellation, cryptococcal meningitis is frequently associated with life-threatening complications and fatal outcomes. Cryptococcus neoformans is a member of the candida family which is ubiquitously found in the soil. However, as it is an opportunistic pathogen, it does not lead to clinical manifestations in immunocompetent individuals. Treatment regimens for cryptococcal sepsis have been described. However, little work has been published on successful treatment and preservation of graft function in kidney transplant (KTX) recipients. Therefore, we report this case of a KTX recipient surviving Cryptococcus sepsis with severe cutaneous manifestations and metastatic dissemination. A 54-year-old male KTX recipient, on long-term immunosuppressive therapy with mycophenolate, prednisolone and tacrolimus, developed severe pain and pink discoloration in his right lower leg after recent venous thrombosis and cytomegalovirus (CMV) colitis. Despite initial antibiotic treatment with piperacillin/tazobactam, his condition worsened, with the emergence of painful blisters (Fig. 1a) and elevated creatinine phosphokinase (CPK) levels. Eventually, bacterial cultures of blister fluid and blood revealed Cryptococcus neoformans. Antimycotic therapy with fluconazole and flucytosine was initiated and further escalated to amphotericin B. However, due to worsening graft function, the initial antimycotic treatment was reestablished. Despite treatment, the patient developed an abscess in the right thenar region (Fig. 2), which was drained by incision. The haemorrhagic fluid of the abscess also showed growth of C. neoformans. An abdominal CT scan revealed several small lesions in both psoas muscles. However, aspiration biopsies did not show any microbial growth. The cutaneous lesions on the right lower leg became necrotic (Fig. 1b), requiring an autologous skin graft (Fig. 1c). After two months, C. neoformans was no longer cultured. The patient improved with continued antimicrobial therapy and was ambulatory after three months. Cryptococcal infection, though rare, can occur in immunocompromised KTX recipients, presenting with atypical manifestations like cutaneous lesions. In our case, diagnosis was challenging due to inadequate initial response to antibiotics, but blood and blister cultures confirmed the infection. Despite pronounced cutaneous lesions, the patients did not suffer from meningitis or any other organ involvement. Treatment required adjustment due to graft dysfunction, highlighting the complexity of managing opportunistic infections in KTX patients.

Abstract Background SPECTRA was a multicenter, observational study of 617 patients (pts) treated with ceftolozane/tazobactam (C/T), to inform the real-world clinical management of gram-negative infections.Table 1.Baseline Characteristics and Microbiology SampleBMI, body mass index; IQR, interquartile range; IV, intravenous; SD, standard deviation, MDR, multidrug-resistant. Methods Retrospective data for pts with an exacerbation of a chronic respiratory infection (CRI) were extracted from medical records < 6 months from the index date, < 30 days from the last dose of C/T, or until death as part of a subcategory analysis. Clinical success, all-cause in-hospital mortality (ACHM), mean length of stay (LOS) in intensive care unit (ICU), and 30-day all-cause re-admission were assessed.Table 2.Treatment OutcomesCI, confidence interval; C/T, ceftolozane/tazobactam; ICU, intensive care unit; IQR, interquartile range; MDR, multidrug-resistant; SD, standard deviation. Results Among 91 pts with CRI exacerbation, 98.9% (n=90/91) had ≥1 comorbidity (mean, 2.6; standard deviation [SD], 1.3), the most common of which was chronic pulmonary disease (81.3%, n=74/91; Table 1). Most pts with microbiology data had infection with multidrug-resistant Pseudomonas aeruginosa (80.3%, n=53/66; Table 1). Median C/T duration was 14.0 days (range: 3–37). Clinical success was seen in 79.1% of pts (n=72/91). Within 28 days of ending treatment, most pts (77.8%, n=56/72) did not require further treatment for the index infection, 81.9% (n=59/72) experienced resolution of CRI exacerbation, 12.1% (n=11/91) experienced microbiological eradication (Table 2). Median ICU LOS was 34.5 days (range: 3–58) in hospitalized pts (n=29). ACHM was 6.6% (n=6/91; 95% confidence interval [CI]: 2.5–13.8). The 30-day all-cause re-admission rate was 15.4% (n=14/91) and was infection-related in 7.7% of pts (n=7/91; Table 2). Conclusion This sub-analysis of the SPECTRA study highlights the clinical characteristics and outcomes of pts hospitalized with CRI exacerbations treated with C/T. The sub-analysis shows positive clinical outcomes of C/T treatment, with high rates of clinical success and resolution of CRI exacerbation. Most patients did not require further antibacterial therapy within 28 days of stopping C/T, achieved clinical stability, and were discharged from the hospital, ICU, or step-down unit. Disclosures Emre Yucel, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) David Paterson, bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Grant/Research Support|Shionogi: Honoraria Florian Thalhammer, MD, MSD: Advisor/Consultant Stefan Kluge, Prof. Dr. med., Merck & Co: Advisor/Consultant|Merck & Co: Board Member Mike Allen, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Brune Akrich, MD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Yanbing Zhou, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company)

Objectives: 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. Methods: SPECTRA was a global, retrospective, observational inpatient study of adults treated with C/T for ≥48 h, 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 hospitalised patients treated with C/T. Results: 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]). Conclusions: 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 To identify occupational subpopulations at risk and predisposing factors for SARS-CoV-2 infections among hospital employees in a large tertiary hospital in Central Europe.Methods In this retrospective observational study, the incidences of SARS-CoV-2 occurring between 2 November 2020 and 1 July 2022, among employees and in the general population, were determined based on real-world data. From the infected personnel, information on sex, age, occupation and vaccination status was obtained and analysed.Results 3812 employees acquired SARS-CoV-2 at least once during the 607-day study period. Particularly high absolute and relative infection rates were noted in staff in operational roles, as demonstrated by 948 infected members or 62.1% of this particular occupational cohort, consisting of 1526 employees. Additionally, infections occurred early in the study period and repeated infections were frequently observed. The numbers of unvaccinated employees were higher and of fully vaccinated employees lower in this occupational group. Vaccinations were further initiated significantly later in the operational staff compared with other occupational groups. Notably, nursing staff and physicians working front line were less frequently tested SARS-CoV-2 positive with 862 out of 3252 (26.5%) and 668 out of 2617 (25.6%) employees, respectively. The weekly epidemic curve in the hospital employees paralleled the observed incidences in the general population, although the proportion of infected was lower in the hospital employees.Conclusions The observed differences in incidences and vaccine acceptance between the individual occupational cohorts showed that providing customised information on disease prevention and vaccination benefits to distinct subgroups is pivotal for hospital management strategies.

This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making.

Abstract Background This sub-analysis of the SPECTRA (Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam [C/T] Real-world Analysis) study aimed to describe the clinical characteristics, treatment patterns, and outcomes of hospitalized adult immunocompromised patients.Table 1. Patient characteristics and Microbiology‡ For patients aged 90 or older the HCP was asked not to enter the exact age and to check a specific box. Therefore, patients aged 90 or older are included in 'Missing' and are not considered in the calculation of mean, median, etc. immunocompromised did not include chronic steroid use, age, or diabetes. Positive culture for more than one organism may apply for one patient. Missing data correspond to patients with no microbiological (MB) sample for index infection, that is without any MB sample performed within +/- 14 days around the index infection with a positive culture result and at least one GN antibacterial tested (whatever the susceptibility result is). Methods SPECTRA was a multicenter observational study conducted in 7 countries, with patients (age≥18yrs) who received ≥48-hours C/T treatment (n=617). Medical records were extracted covering a 6-month period prior to the index date, up to 30 days after the last dose of C/T or until death. All-cause in-hospital mortality (ACHM), clinical success, ICU admission, microbiology results, and treatment patterns in immunocompromised patients (IP, n=268) are reported. Immunocompromised patients were defined as patients with a Hematologic Malignancy or Solid Tumor or recipient of transplant. Transplant patients (TP) was 60% (n=160).Table 2. Clinical Outcomes: All-Cause In-Hospital Mortality and Clinical Success*Bile duct anostomic leakage, CMV infection, Post-operative Complication, Digestive hemorrhage, Invasive fungal infection, C difficile colitis(1) More than one criterion may apply for one patient. Results Median age was 57 (IP) and 50.5 years (TP). 66% and 67.5% were male, respectively.28.4% had respiratory-related infections (RRI), 22.7% had sepsis, 27.6% had septic shock, 13.4% had Cystic Fibrosis, 29.4% had pneumonia, 2.6% had bone and joint infection. ACHM was 24% for IP, and 23% for TP. Time from index date to death was a median of 29 and 35, respectively. Leading causes of death were sepsis (31%), multiorgan failure (29%), cancer (12%) for IP. Clinical success was 62.7% for IP. 84% (143/170) were Pseudomonas aeruginosa (PsA), and MDR PsA was 71.8% (n=122). 38.7% (n=98) received optimal dose. Up to 50% of the patients were admitted to ICU during the index hospitalization (n=133), and 46% of the ICU admissions were related to index infection. Median length of stay at ICU was 13 days.Table 3.Treatment patterns and Intensive Care Unit (ICU) Conclusion Treatment with C/T resulted in a high rate of clinical success in this real-world cohort of immunosuppressed patients, despite dosing that frequently deviated from labelled dosing. Pseudomonas aeruginosa including MDR isolates were frequently identified. Based on these results C/T is a useful option for the treatment of GN infections including those due to MDR PsA in the immunosuppressed patient population. Disclosures Emre Yucel, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) David Paterson, bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Grant/Research Support|Shionogi: Honoraria Florian Thalhammer, MD, MSD: Advisor/Consultant Stefan Kluge, Prof. Dr. med., Merck & Co: Advisor/Consultant|Merck & Co: Board Member Mike Allen, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Brune Akrich, MD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Yanbing Zhou, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company)