Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60–4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients. Study registration number: NCT03919032Fil: Marciano, Sebastián. Hospital Italiano; ArgentinaFil: Gutierrez Acevedo, Maria N.. Hospital 4 de Junio; ArgentinaFil: Barbero, Sabrina. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: del C. Notari, Lorena. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Agozino, Marina. Sanatorio Guemes; ArgentinaFil: Fernandez, Jose L.. Sanatorio Guemes; ArgentinaFil: Anders, Maria M.. Hospital Alemán; ArgentinaFil: Grigera, Nadia. Hospital Alemán; ArgentinaFil: Antinucci, Florencia. Hospital Alemán; ArgentinaFil: Orozco Ganem, Orlando F.. Hospital Aleman; ArgentinaFil: Murga, Maria D.. Hospital A. C. Padilla; ArgentinaFil: Perez, Daniela. Hospital A. C. Padilla; ArgentinaFil: Palazzo, Ana. Hospital A. C. Padilla; ArgentinaFil: Martinez Rejtman, Liria. Hospital Teodoro J. Schestakow; ArgentinaFil: Duarte, Ivonne G.. Hospital 4 de Junio; ArgentinaFil: Vorobioff, Julio. Hospital Provincial del Centenario; ArgentinaFil: Trevizan, Victoria. Hospital Provincial del Centenario; ArgentinaFil: Bulaty, Sofía. Hospital Provincial del Centenario; ArgentinaFil: Bessone, Fernando. Hospital Provincial del Centenario; ArgentinaFil: Valverde, Marcelo. Hospital de Clinicas Dr. Manuel Quintela; UruguayFil: Elizondo, Martín. Hospital de Clinicas Dr. Manuel Quintela; UruguayFil: Bosia, José D.. Hospital Prof. Rodolfo Rossi, la Plata; ArgentinaFil: Borzi, Silvia M.. Hospital Prof. Rodolfo Rossi, la Plata; ArgentinaFil: Stieben, Teodoro E.. Provincia de Entre Rios. Hospital San Martin; ArgentinaFil: Masola, Adriano. Provincia de Entre Rios. Hospital San Martin; ArgentinaFil: Ramos, Agñel. Sanatorio Parque; ArgentinaFil: Pages, Josefina. Universidad Austral; ArgentinaFil: Tevez, Silvina. Sanatorio Guemes; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Giunta, Diego Hernan. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

PLUS-IS-LESS project: Procalcitonin and Lung UltraSonography-based antibiotherapy in patients with Lower rESpiratory tract infection in Swiss Emergency Departments: study protocol for a pragmatic stepped-wedge cluster-randomized trial

Abstract Background Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED). Methods The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning. Discussion The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful. The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance. Trial registration This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406. Trial status Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023

Additional file 1 of PLUS-IS-LESS project: Procalcitonin and Lung UltraSonography-based antibiotherapy in patients with Lower rESpiratory tract infection in Swiss Emergency Departments: study protocol for a pragmatic stepped-wedge cluster-randomized trial

Additional file 1. SPIRIT Checklis