Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

Bloodstream infections in older population: epidemiology, outcome, and impact of multidrug resistance.

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated.

Impact of a medication reconciliation care bundle at hospital discharge on continuity of care: A randomised controlled trial.

OBJECTIVE: To compare the impact of a care bundle including medication reconciliation at discharge by a pharmacist versus standard of care, on continuity of therapeutic changes between hospital and primary care and outcome of patients, within 1 month after discharge. METHODS: Randomised controlled trial in 120 adult patients with at least one chronic disease and three current medications before admission, hospitalised in an infectious disease department of a tertiary hospital and discharged home. Patients were randomly assigned (1:1) to receive a discharge care bundle including medication reconciliation, counselling session and documentation transfer to primary care physician (PCP) (intervention group) or standard of care (control group). Primary outcome was the proportion of in-hospital prescription changes, not maintained by the PCP, 1 month after discharge. Secondary outcome measures included the proportion of patients experiencing early PCP's consultation, hospital readmissions or adverse reactions within 1-month postdischarge and cost of discharge prescriptions. RESULTS: Baseline characteristics were comparable between the two groups. One month after discharge, the proportion of in-hospital prescription changes, not maintained by the PCP, was 11% in the intervention group versus 24% in the control group (P = .007). The median delay before PCP's consultation was longer in the intervention group (30.5 vs 19.5 days, P = .013), there were fewer patients readmitted to hospital (3.4% vs 20.7%, P = .009, odds ratio (OR) = 0.13 [0.02-0.53]) and fewer patients who suffered from adverse drug reaction (7.0% vs 22.8%, P = .04, OR = 0.26 [0.07-0.78]). CONCLUSION: This care bundle resulted in the reduction of treatment changes between hospital discharge and primary care.

Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial.

BACKGROUND: Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. METHODS: Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. RESULTS: Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5-2.5) in the WOCA group versus 2.5 (1.2-4.0) (P = .0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P < .001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0-2.0) versus 3.0 (2.0-5.0) (P = .004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. CONCLUSIONS: WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. CLINICAL TRIALS REGISTRATION: NCT01388413.

Monomicrobial bone and joint infection due to Corynebacterium striatum: literature review and amoxicillin-rifampin combination as treatment perspective.

Corynebacterium striatum is a ubiquitous colonizer of human skin and mucous membranes. It is increasingly involved in infections, especially with prosthetic devices or in immunocompromised individuals. Microbiological diagnosis is challenging and bacterial resistance is a major concern. We performed a retrospective study of monomicrobial bone and joint infections (BJI) due to C. striatum in two referral centers from April 2012 to July 2017. We collected the patients' clinical and microbiological characteristics and outcomes. We also performed a literature review of BJI due to C. striatum. We identified 12 cases (nine prosthetic joint infections, one osteosynthetic device infection, one non-union, and one arthritis) in 11 patients, five of which were immunocompromised. Microbiological diagnosis was performed with prolonged culture media. Ten out of 12 strains were susceptible to aminopenicillin, a drug class not recommended for testing by the EUCAST/CASFM guidelines, and 8/12 patients were treated with amoxicillin-rifampicin. The cure rate was 8/12, after a median follow-up period of 487.5 days (IQR 140.3-1348.5). Twelve cases of BJI due to C. striatum were previously reported. Among them, 5/12 patients were immunocompromised, 3/12 cases were acute BJI, and 2/12 were device-related infections. The diagnosis was performed by PCR in one case, and 10/12 patients were treated with glycolipopeptides, with a cure rate of 11/12. We report the largest cohort of monomicrobial BJI with C. striatum. Determination of aminopenicillin susceptibility is essential since it is frequently active in our experience, even in BJI. The cure rate of this infection seems high.

Case of femoral pseudarthrosis due to Scedosporium apiospermum in an immunocompetent patient with successful conservative treatment and review of literature.

Scedosporium apiospermum is a ubiquitous filamentous fungus, commonly found in soil, sewage and polluted waters. It is rarely pathogenic but can cause a broad spectrum of clinical diseases, which can be localised or disseminate to distant organs. The disseminated form of the disease is mostly seen among immunocompromised patients. However, some rare cases of disseminated disease have been reported in immunocompetent individuals. Treatment of these infections is challenging because of their natural resistance to many antifungal agents. Here, we report the case of a 57-year-old immunocompetent patient diagnosed with femoral pseudarthrosis due to S. apiospermum, despite having no obvious clinical sign of infection. Previously, the patient had undergone four iterative femoral surgeries following a road traffic accident which occurred 20 years before. During its last surgery for pseudarthrosis, no clinical or biological signs of infection were present. Per operative samples tested positive for S. apiospermum. The patient was successfully treated with oral voriconazole during 6 months with an excellent tolerance. We also provide a review of literature on bone and joint infections due to Scedosporium spp. (S. apiospermum, Scedosporium boydii and Scedosporium aurantiacum), discussing the evolution of their management and outcome which seems to improve since the use of voriconazole.

Management of febrile urinary tract infection among spinal cord injured patients.

BACKGROUND: Urinary tract infection (UTI) among patients with neurogenic bladder is a major problem but its management is not well known. We studied the relationship between antibiotic regimen use and the cure rate of those infections among 112 patients with neurogenic bladder. METHODS: We studied a retrospective cohort of febrile UTI among patients with neurogenic bladder. Drug selection was left to the discretion of the treating physicians, in accordance with current guidelines. Patients were divided into 3 groups according to antibiotic treatment duration (<10 days, between 10 and 15 days, and >15 days). We analysed clinical and microbiogical cure rate one month after the end of antibiotic treatment. RESULTS: The three groups of patients were similar, especially in terms of drug treatment (equal distribution). The cure rates were not significantly different (71.4 %, 54.2 %, and 57.1 %, respectively; p = 0.34). Moreover, there was no difference in cure rate between mono and dual therapy (44 % for monotherapy vs. 40 % for dual therapy; p = 0.71). CONCLUSION: This descriptive study supports the efficacy of antimicrobial treatment duration of less than 10 days and the use of monotherapy to treat febrile UTI among patients with neurogenic bladder. A randomized control trial is required to confirm these data.

Should we, and how to, optimize cefiderocol administration during severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumanii? A viewpoint.

INTRODUCTION: Acinetobacter baumannii is classified by the Center for Disease Control and Prevention (CDC) as an "urgent threat" due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii METHODS: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol. DISCUSSION: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol's entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes. CONCLUSION: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.

Real-life impact on antimicrobial prescription of Syndromic Molecular Testing in adults hospitalized in infectious disease departments. Respiratory Syndromic Molecular Testing panel: Is it worth it?

BACKGROUND: While sensitive molecular diagnostic tests enable accurate and rapid diagnosis of many respiratory viruses, their impact on antibiotic management remains uncertain. Our study aimed to evaluate the impact of respiratory syndromic molecular testing panel in real-life clinical practice. METHOD: Retrospective descriptive study involving consecutive hospitalized patients in an infectious disease department who had been prescribed a respiratory syndromic molecular testing panel on nasopharyngeal swab samples (FilmArray Respiratory Panel 2 plus) during hospitalization from October 1st, 2021, to February 28th, 2023. RESULTS: All in all, 94 out of 210 screened patients were included in the study. Syndromic molecular testing results influenced antibiotic treatment in seven cases: discontinuation in four cases (three virus identifications), changes in two (Mycoplasma pneumoniae positive cases), and initiation in two (negative viral PCRs and one positive bacterial culture). CONCLUSION: In our study, respiratory syndromic molecular testing had low impact on antibiotic modification.

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Antibiotic Consumption and Bacterial Resistance Rates in Hospitalized COVID-19 Patients: A Retrospective Study During the 3 First Surges.

In our hospital, during COVID-19 pandemic, overall consumption of antibiotics increased during the three first surges, mainly due to ICU prescription However, antibiotic consumption decreased in the Infectious Diseases Department. Rates of ESBL Enterobacterales remained stable.

Digital health for remote home monitoring of patients with COVID-19 requiring oxygen: a cohort study and literature review.

Background: The clinical course and outcome of COVID-19 vary widely, from asymptomatic and mild to critical. Elderly patients and patients with comorbidities are at increased risk of respiratory failure and oxygen requirements. Due to the massive surge, the pandemic has created challenges for overwhelmed hospitals. Thus, the original home management of COVID-19 patients requiring oxygen and remote monitoring by a web app and a nurse at home were implemented in our center. We aimed to evaluate the outcome of patients with COVID-19 requiring oxygen who benefited from home remote monitoring management. Methods: We performed a retrospective cohort study on all COVID-19 patients requiring oxygen (< 5 L/min) who consulted from October 2020 to April 2021 at our emergency department and were managed with home remote monitoring by a web app and an in-home nurse. We also carried out a literature review of studies on COVID-19 patients requiring oxygen with remote monitoring. Results: We included 300 patients [184 (61.3%) male patients, median age 51 years]. The main comorbidities were cardiovascular disease (n = 117; 39.0%), diabetes mellitus (n = 72; 24.0%), and chronic respiratory disease (n = 32; 10.7%). Among the 28 (9.3%) patients readmitted to the hospital, 6 (1.9%) were hospitalized in the intensive care unit, and 3 (0.9%) died. In the multivariable analysis, risk factors for unplanned hospitalization were chronic respiratory failure (odds ratio (OR) =4.476, 95%CI 1.565-12.80), immunosuppression (OR = 3.736, 95%CI 1.208-11.552), and short delay between symptoms onset and start of telemonitoring (OR = 0.744, 95%CI 0.653-0.847). In the literature review, we identified seven other experiences of remote monitoring management. Mortality rate and unplanned hospitalization were low (maximum 1.9 and 12%, respectively). Conclusion: Our study confirms the safety of home remote monitoring of patients with COVID-19 who require oxygen, as well as our literature review. However, patients with chronic respiratory failure and immunosuppression should be closely monitored.

Short Antibiotic Treatment Duration for Osteomyelitis Complicating Pressure Ulcers: A Quasi-experimental Study.

Background: Osteomyelitis-complicating pressure ulcers are frequent among patients with spinal cord injuries (SCIs), and the optimal management is unknown. In our referral center, the current management is debridement and flap coverage surgeries, followed by a short antibiotic treatment. We aimed to evaluate patients' outcomes a year after surgery. Methods: We performed a quasi-experimental retrospective before/after study on SCI patients with presumed osteomyelitis associated with perineal pressure ulcers. We included all patients who underwent surgery with debridement and flap covering, followed by effective antibiotic treatment, between May 1, 2016, and October 30, 2020. The effective antimicrobial treatment duration included the 10 days leading up to January 1, 2018 (before period), and the 5 to 7 days after (after period). We also compared the efficacy of 5-7-day vs 10-day antibiotic treatment and performed uni- and multivariable analyses to identify factors associated with failure. Results: Overall, 415 patients were included (77.6% male patients; mean age ± SD, 53.0 ± 14.4 years). Multidrug-resistant organisms (MDROs) were involved in 20.7% of cases. Favorable outcomes were recorded in 69.2% of cases: 117/179 (65.3%) in the 10-day treatment group vs 169/287 (71.9%) in the 5-7-day treatment group (P = .153). The only factor associated with failure in the multivariate analysis was a positive culture from suction drainage (odds ratio, 1.622; 95% CI, 1.005-2.617; P = .046). Effective treatment duration >7 days and intraoperative samples negative for MDROs were not associated with better outcomes (P = .153 and P = .241, respectively). Conclusions: A treatment strategy combining surgical debridement and flap covering, followed by 5 to 7 days of effective antibiotic treatment seems safe.

A Restructured Hospital Into a One-Building Organization for COVID-19 Patients: A Resilient and Effective Response to the Pandemic.

The COVID-19 pandemic is a unique crisis challenging healthcare institutions as it rapidly overwhelmed hospitals due to a large influx of patients. This major event forced all the components of the healthcare systems to adapt and invent new workflows. Thus, our tertiary care hospital was reorganized entirely. During the cruising phase, additional staff was allocated to a one-building organization comprising an intensive care unit (ICU), an acute care unit, a physical medicine and rehabilitation unit, and a COVID-19 screening area. The transfer of patients from a ward to another was more efficient due to these organizations and pavilion structure. The observed mortality was low in the acute care ward, except in the palliative unit. No nosocomial infection with SARS-CoV-2 was reported in any other building of the hospital since this organization was set up. This type of one-building organization, integrating all the components for comprehensive patient care, seems to be the most appropriate response to pandemics.