Reply to Paranhos-Baccalà et al. Comment on "Cuesta et al. An Assessment of a New Rapid Multiplex PCR Assay for the Diagnosis of Meningoencephalitis. Diagnostics 2024, 14, 802".

We appreciate the interest and reflections of Paranhos-Baccalà and colleagues in our recent article published in Diagnostics [...].

Performance of an Autonomous Sanitary Sterilisation Ultraviolet Machine (ASSUM) on terminal disinfection of surgical theaters and rooms of an intensive-intermediate care unit.

Background: Ultraviolet- C (UV-C) light is effective for reducing environmental bioburden in hospitals, and the use of robots to deliver it may be advantageous. Aim: To evaluate the feasibility and clinical efficacy of an autonomous programmable UV-C robot in surgical and intensive care unit (ICU) rooms of a tertiary hospital. Method: During ten consecutive months, the device was used in six theatres where cardiac, colorectal and orthopaedic surgeries were performed, and in the rooms previously occupied by patients subjected to contact precautions of a 14-bed ICU. Surgical site infection (SSI) rates of procedures performed in the UV-cleaned theatres were compared with those of the previous year. Incidence in clinical samples of ICU-acquired multiple-drug resistant (MDR) microorganisms was compared with that of the same period of the previous year. An UV-C exposure study done by semi-quantitative dosimeters and a survey of the bioburden on surfaces were carried out. Findings: SSI rates in the pre- and post-intervention periods were 8.67% (80/922) and 7.5% (61/813), respectively (p=0.37). Incidence of target microorganisms in clinical samples remained unchanged (38.4 vs. 39.4 per 10,000 patient-days, p=0.94). All the dosimeters exposed to ≤1 meter received ≥500 mJ/cm2. The bacterial load on surfaces decreased after the intervention, particularly in ICU rooms (from 4.57±7.4 CFU to 0.27±0.8 CFU, p<0.0001). Conclusion: Deployment of an UV-C robot in surgical and ICU rooms is feasible, ensures adequate delivery of germicidal UV-C light and reduces the environmental bacterial burden. Rates of surgical site infections or acquisition of MDR in clinical samples of critically-ill patients remained unchanged.

Cervical spine spondylodiscitis due to neglected esophageal perforation after a dilation procedure 30 years after a laringectomy and radiotherapy. Report of a case and review of literature.

Current treatment of cervical spine spondylodiscitis generally involves a radical surgical debridement and stable reconstruction together with antibiotic therapy until complete healing. But this classical approach could be difficult for patients who have been treated previously for an esophageal carcinoma and received radiotherapy. We present a case of a 75-year-old male who underwent an esophageal dilation procedure and developed afterward a spondylodiscitis with epidural abscess due to a neglected esophageal perforation. Blood cultures were positive for Peptostreptococcus. Cervical spondylodiscitis and epidural abscess are extremely rare complications of esophageal dilations. Successful treatment without debridement was achieved by performing a posterior fixation without decompression associated with antibiotic therapy for 8 weeks. The present case highlights that spondylodiscitis and epidural abscess may be treated in selected cases where the anterior neck is unapproachable and with a recognized pathogen by a posterior approach fixation without debridement, in association to specific antibiotic therapy.

Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.

BACKGROUND: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. METHODS: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. RESULTS: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). CONCLUSIONS: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

Prevalence and impact of multidrug-resistant bacteria in solid cancer patients with bloodstream infection: a 25-year trend analysis.

The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes. IMPORTANCE: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

Isolation of Staphylococcus pseudintermedius in Immunocompromised Patients from a Single Center in Spain: A Zoonotic Pathogen from Companion Animals.

Staphylococcus pseudintermedius, a commensal opportunistic bacterium predominantly residing in the skin of companion animals, particularly dogs, has the potential to induce skin and soft tissue infections in pets, and zoonotic infections, including catheter-related complications. This study documents four cases of S. pseudintermedius infection or colonization in patients who had close contact with dogs or cats. Identification of the bacterial species was performed using MALDI-TOF mass spectrometry, and antibiotic susceptibility was determined using microdilution assay. DNA was sequenced using Nanopore technology followed by in silico analysis. Three isolates were multidrug resistant, including resistance to methicillin, with one belonging to the prevalent European lineage ST551, and the other two were attributed to a novel multilocus sequence type, ST2672. The remaining isolate was attributed to the novel multilocus sequence type ST2673 and was methicillin susceptible. All four isolates exhibited an array of virulence factors that contributed to colonization, damage to host immune cells, and biofilm formation. All the ST551 isolates included in the comparative analysis displayed clonality within the European continent. The importance of describing zoonotic infections associated with S. pseudintermedius resides in the scarcity of available scientific literature, further accentuated by its heightened resistance profile and potential complications, particularly in the context of catheter-related infections.

Corrigendum: C-reactive protein isoforms as prognostic markers of COVID-19 severity.

[This corrects the article DOI: 10.3389/fimmu.2022.1105343.].

Real-World Use and Treatment Outcomes of Ceftaroline Fosamil in Patients with Complicated Skin and Soft Tissue Infection: A Multinational Retrospective Study.

Background: Ceftaroline fosamil is approved for the treatment of complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP); however, data on its real-world use and effectiveness in Europe and Latin America are currently limited. This retrospective observational study assessed ceftaroline fosamil use and treatment outcomes in adults hospitalized with cSSTI or CAP treated with ceftaroline fosamil in a usual care setting in Europe and Latin America. Results for patients with cSSTI are reported. Methods: Data from patients with cSSTI who received ≥4 consecutive intravenous ceftaroline fosamil doses up to May 31, 2019, were collected from sites in Brazil, Colombia, France, Greece, Italy, and Spain. Patient characteristics, clinical management, hospitalization information, microbiological diagnosis, and clinical responses were summarized descriptively. Healthcare resource use variables were evaluated by clinical response to ceftaroline fosamil. Results: Data for 132 patients were included (58.3% male; mean age 58.5 years). Most common lesions were cellulitis/fasciitis (62.1%), abscess (34.1%), and post-surgical wounds (19.7%). Pathogens most frequently identified were methicillin-resistant (18.2%) and methicillin-susceptible Staphylococcus aureus (17.4%). Median (range) ceftaroline fosamil treatment duration was 8 (2-60) days (daily doses of 1200 [400-2400] mg); 78 patients (59.1%) received monotherapy. In total, 75 (56.8%) patients had additional antibiotics after ceftaroline fosamil. Clinical response occurred in 118 (89.4%) patients. All-cause 30-day readmission occurred in 13 (9.8%) patients, and all-cause 30-day mortality in 7 (5.3%). Clinical response to ceftaroline was associated with >25% shorter length of hospital and intensive care stay, and with ~40% lower hospital costs, versus non-responders. Conclusion: Ceftaroline fosamil was effective in treating adults with cSSTI and clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders, in Europe and Latin America. Clinicaltrialsgov Identifier: NCT04198571.

Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [-13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [-16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [-0.2%, 40.2%]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Prevalence and Impact of Unexpected Positive Intraoperative Cultures in Total Hip or Knee Revision Surgery.

BACKGROUND: Our aim was to evaluate the prevalence and impact of unexpected positive intraoperative cultures (UPICs) on the outcome of presumed aseptic total knee and hip revision surgery. METHODS: Data regarding patients who underwent elective total hip or knee revision surgery from January 2003 to July 2017 due to preoperatively presumed aseptic reasons was retrospectively reviewed. Partial revisions and patients who had follow-ups below 60 months were excluded from the study. In all surgeries, at least 3 intraoperative samples were taken for microbial culture. Failure was defined as the need for rerevision due to any cause at 5 years and/or the need for antibiotic suppressive therapy. Overall, 123 total hip and 431 total knee revisions were eligible for the study. All cases had at least a 5 years follow-up. RESULTS: There were 420 cases (75.8%) that had all cultures negative, 108 (19.5%) had a single UPIC, and 26 (4.7%) had either ≥2 UPICs for the same microorganism or 1 UPIC for a virulent microorganism. This latter group was not associated with a significantly higher failure rate (2 of 26, 7.7%) compared to those in the aseptic group (54 of 528, 10.2%). Revisions performed within the first 24 months after primary implantation had a higher 5-years rerevision rate (19.3 versus 8.4%, P = .01), mainly attributable to aseptic causes. CONCLUSIONS: Total hip and knee revisions with UPICs were not significantly associated with a higher rerevision risk at 5 years. Those revisions performed within the first 24 months after primary arthroplasty had a higher rate of any-cause failure.

Chimeric Antigen Receptor T-Cell Postinfusion Fever: Infection Profile, Clinical Parameters, and Biomarkers Trends to Assist Antibiotic Stewardship.

Background: This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship. Methods: This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described. Results: Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2-5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented. Conclusions: Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post-CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics.

Extended remdesivir administration in haematological patients with malignancies and COVID-19 during the Omicron era: safety and outcomes.

OBJECTIVES: To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined. METHODS: We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity. RESULTS: From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6-3.9) (min-max 1.6-8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode. CONCLUSIONS: The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients.

The Management of Patients at High Risk of Serious COVID-19 Disease: Optimising the Patient Pathway in the Middle East, Africa, and Eastern Europe.

Introduction For patients at high risk of severe COVID-19 disease, antiviral therapeutic options are available to reduce the risk of hospitalization or death. Although many countries have developed national guidelines for COVID-19 management that include use of antiviral agents, it is unclear how these guidelines are used in daily clinical practice. This study aims to assess the management of high-risk COVID-19 patients in the Middle East, Africa, and Eastern Europe, with a focus on understanding current practices, challenges, and potential strategies for improvement. Methods Healthcare professionals (HCPs) from the Middle East, Africa, and Eastern Europe came together at a regional summit in February 2023 to share perspectives on the therapeutic management of patients at high risk of serious COVID-19 disease in the community. Summit participants represented diverse medical specialties, geographical regions, and healthcare settings. Key insights gathered during the summit were supplemented with evidence from the published literature via a non-systematic literature search of MEDLINE and online sources such as government reports since the start of 2020 to identify articles on disease burden, unmet needs, treatment access, antiviral therapy, guidelines related to individuals with COVID-19 at high-risk for poor outcomes in low- and middle-income countries (LMICs). Together, these sources were used by the authors to generate their recommendations for future priorities and optimal care pathways globally. Results Specific insights gathered from the summit were that participants reported that primary care is the first point of contact for high-risk patients, but the role of primary care physicians (PCPs) in treatment is uncertain. Additionally, participants highlighted that between-country differences in the care pathway for high-risk patients are due to variations in local treatment practices, healthcare system structures, and resourcing. In line with the published literature, participants agreed that HCP education is needed to support the identification, counseling, and appropriate management of high-risk patients and that pharmacists have a critical role to play in identifying clinically important potential interactions with antiviral treatment and recommending appropriate adjustments. Furthermore, patient hesitancy can result in late presentation, delayed treatment, and potential progression of symptoms. HCPs should proactively counsel high-risk patients, so they are aware of their risk and its implications and understand what to do if they experience symptoms of COVID-19. Targeted educational initiatives for patients are needed to mitigate reluctance to undergo COVID-19 testing and counter COVID-19 misinformation. Conclusion Collaboration among stakeholders is essential to optimize COVID-19 management for high-risk patients globally, ensuring effective implementation of guidelines and improving outcomes.

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain.

OBJECTIVES: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. METHODS: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. RESULTS: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. CONCLUSION: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections.

Background: The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods: We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results: The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79-2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11-1.15; P = .09), which also had the highest risk of treatment failure. Conclusions: The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Ceftaroline fosamil treatment patterns and outcomes in adults with community-acquired pneumonia: a real-world multinational, retrospective study.

Background: This multicentre, observational, retrospective chart review study assessed ceftaroline fosamil treatment patterns and outcomes in adults hospitalized with community-acquired pneumonia (CAP) in usual care settings. Methods: Anonymized patient data were extracted from hospital records of adults with CAP who received ≥4 consecutive IV ceftaroline fosamil doses at sites in Brazil, Colombia, France, Greece, Italy, Russia and Spain. Results: The dataset included 185 patients (58.9% male; mean age 62.2 years), of whom 128 (69.2%) had severe CAP defined by CURB-65, PSI/PORT score or physician judgement. Streptococcus pneumoniae (n = 44; 23.8%) and Staphylococcus aureus [MSSA (n = 15) and MRSA (n = 14)] were the most frequently identified pathogens. Clinical response occurred in 151 (81.6%) patients overall, and in 104 (81.3%) severe CAP patients. Response within ≤4 and >4 days occurred in 79 (42.7%) and 62 (33.5%) patients (unknown, n = 10), respectively. Twenty (10.8%) patients required readmission within 30 days. Thirty-day all-cause mortality rates were 9.7% (n = 18) overall and 10.2% (n = 13) in severe CAP. In sensitivity analysis using ICU admission as a more objective marker of severe CAP (n = 75), clinical response and 30 day mortality occurred in 57 (76.0%) and 10 (13.3%) patients, respectively. Overall, clinical response to ceftaroline fosamil was associated with >60% shorter length of ICU stay (3.6 versus 9.2 days), and >30% lower hospital costs ($8449 versus $12 559) versus non-responders. Conclusions: Ceftaroline fosamil was effective in treating adults with CAP, including severe CAP, in Europe and Latin America. Clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders.

Utility of SARS-CoV-2 Subgenomic RNA in Kidney Transplant Recipients Receiving Remdesivir.

INTRODUCTION: There is no reliable microbiological marker to guide responses to antiviral treatment in kidney transplant recipients (KTR) with COVID-19. We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) RT-PCR before and after receiving treatment with remdesivir compared with genomic RNA (gRNA) RT-PCR and its use as a surrogate marker of viral replication. METHODS: We analyzed gRNA and sgRNA at baseline and after remdesivir treatment in KTR who received remdesivir for SARS-CoV-2 infection from November 2021 to February 2022. RESULTS: Thirty-four KTR received remdesivir for SARS-CoV-2 infection. The median time since transplantation was 80 months (IQR 3-321) and 75% of patients had previously received 3 doses of a mRNA SARS-CoV-2 vaccine. Three patients (8%) were classified with mild, 25 (73%) with moderate, and 6 (17%) with severe SARS-CoV-2 infection. Thirty-two (94%) patients received 5 doses of remdesivir and two patients received 2 doses. The median time between symptom onset to remdesivir treatment was 5 days (IQR 3-8.5). The median days of hospitalization were 6 (IQR 2-112). gRNA was positive in all patients at baseline and after remdesivir. Five (15%) patients had negative sgRNA at baseline and 20 (59%) after receiving remdesivir. Patients presenting with negative sgRNA at baseline were discharged from hospital in ≤ 6 days without complications. Moreover, those with negative sgRNA after remdesivir therapy did not require ICU admission and had favorable outcomes. Nevertheless, patients with positive sgRNA after antiviral treatment presented worse outcomes, with 47% requiring ICU admission and the three (9%) recorded deaths in the study were in this group. CONCLUSIONS: Based on these data, we hypothesize that sgRNA may have clinical utility to help monitor virologic response more accurately than gRNA in KTR who receive remdesivir. Moreover, patients with negative sgRNA at baseline may not require antiviral treatment and others presenting positive sgRNA at day 5 could benefit from prolonged or combined therapies.

Emergence of carbapenem-resistant Pseudomonas aeruginosa ST179 producing both IMP-16 and KPC-2: a case study of introduction from Peru to Spain.

We describe four cases of a novel carbapenem-resistant Pseudomonas aeruginosa ST179 clone carrying the blaKPC-2 or blaKPC-35 gene together with blaIMP-16, imported from Peru to Spain and isolated from leukemia patients. All isolates were multidrug-resistant but remained susceptible to fosfomycin, cefiderocol, and colistin. Whole-genome sequencing revealed that blaKPC-2 and blaKPC-35 were located in an IncP6 plasmid, whereas blaIMP-16 was in a chromosomal type 1 integron. This study highlights the global threat of multidrug-resistant P. aeruginosa clones and underscores the importance of monitoring and early detection of emerging resistance mechanisms to guide appropriate treatment strategies. The importation and spread of such clones emphasize the urgent need to implement strict infection control measures to prevent the dissemination of carbapenem-resistant bacteria. IMPORTANCE: This is the first documented case of a Pseudomonas aeruginosa ST179 strain carrying the blaKPC-35 gene, and it represents the first report of a P. aeruginosa co-harboring blaIMP-16 and either blaKPC-2 or blaKPC-35, which wre imported from Peru to Spain, highlighting a threat due to the capacity of spreading carbapenem-resistance via plasmid conjugation.

Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018-2022.

OBJECTIVES: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. METHODS: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. ß-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. RESULTS: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. CONCLUSION: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship.