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.

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.

Actinomycetoma Caused by Actinomadura mexicana, A Neglected Entity in the Caribbean.

Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of actinomycetoma caused by Actinomadura mexicana in the Caribbean region.

Comparison of physiological markers, behavior monitoring, and clinical illness scoring as indicators of an inflammatory response in beef cattle.

Clinical illness (CI) scoring using visual observation is the most widely applied method of detecting respiratory disease in cattle but has limited effectiveness in practice. In contrast, body-mounted sensor technology effectively facilitates disease detection. To evaluate whether a combination of movement behavior and CI scoring is effective for disease detection, cattle were vaccinated to induce a temporary inflammatory immune response. Cattle were evaluated before and after vaccination to identify the CI variables that are most indicative of sick cattle. Respiratory rate (H2 = 43.08, P < 0.0001), nasal discharge (H2 = 8.35, P = 0.015), and ocular discharge (H2 = 16.38, P = 0.0003) increased after vaccination, and rumen fill decreased (H2 = 20.10, P < 0.0001). Locomotor activity was measured via leg-mounted sensors for the four days preceding and seven days following vaccination. A statistical model that included temperature, steps, lying time, respiratory rate, rumen fill, head position, and excess saliva was developed to distinguish between scores from before and after vaccination with a sensitivity of 0.898 and specificity of 0.915. Several clinical illness signs were difficult to measure in practice. Binoculars were required for scoring respiratory rate and eye-related metrics, and cattle had to be fitted with colored collars for individual identification. Scoring each animal took up to three minutes in a small research pen; therefore, technologies that can automate both behavior monitoring and identification of clinical illness signs are key to improving capacity for BRD detection and treatment.

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.

Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review.

OBJECTIVES: Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition. METHODS: All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed. RESULTS: Seventeen patients were included. Bacteria were identified in 16 cases: Staphylococcus aureus (n = 10), including methicillin-resistant S. aureus (n = 1); and coagulase-negative staphylococci (n = 10), including methicillin-resistant Staphylococcus epidermidis (n = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0-476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%. CONCLUSION: Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

Treatment of bone and joint infections by ceftazidime/avibactam and ceftolozane/tazobactam: a cohort study.

OBJECTIVES: Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) are two novel antibacterials with known efficacy against Gram-negative bacteria (GNB). We aimed to describe the efficacy and safety of surgical management combined with C/A or C/T treatment for bone and joint infections (BJIs). METHODS: We conducted an observational, bicentric study of patients treated with C/A or C/T for a BJI between May 2016 and June 2019. Failure was defined as the need for unplanned additional antibiotic treatment or orthopaedic surgery, or death due to the BJI up to the patient's latest visit. RESULTS: Overall, 15 patients were included. Nine patients were treated with C/A, mainly for polymicrobial BJI due to multidrug-resistant (MDR) bacteria (Enterobacteriaceae, n = 7). Six patients were male, the median age was 66 years and the median Charlson comorbidity index (CCI) was 5. It was the first septic episode at the site in 3/9 patients. The cure rate was 7/9 (median follow-up, 272 days). Two patients showed C/A-related confusion. Five patients were treated with C/T for BJI involving MDR Pseudomonas aeruginosa. Four patients were male, the median age was 53 years and the median CCI was 2. All patients had previous septic episodes at the infection site. The cure rate was 3/5 (median follow-up, 350 days). One patient was successfully treated by C/T then C/A for multistage spondylodiscitis. CONCLUSION: In our experience, C/A and C/T are two effective and safe options, even as salvage treatment for BJI due to MDR-GNB despite the absence of label, however more data are warranted.

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective: To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions: Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive ß-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures: The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of ß-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results: Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.

Clinical Cutaneous Features of Patients Infected With SARS-CoV-2 Hospitalized for Pneumonia: A Cross-sectional Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a current pandemic worldwide. This virus can reach all organs and disturbs the immune system, leading to a cytokine storm in severe forms. We aimed to report cutaneous features among coronavirus disease 2019 (COVID-19) hospitalized patients. METHODS: We performed a cross-sectional study on 1 given day among all patients hospitalized in acute care for COVID-19 and included all patients with cutaneous features. Follow-up 48 hours later was obtained. RESULTS: Among 59 adult patients hospitalized on the day of the study in an infectious diseases ward for SARS-CoV-2 infection who were confirmed by molecular assay and/or radiological findings (computed tomography scan), 40 were included. Several cutaneous manifestations were found: macular exanthema (80%), face edema (32%), livedo (13%), urticarial rash (8%), purpura (5%), oral lichenoid lesions (33%), and conjunctivitis (18%). Cutaneous biopsy was performed in 17 patients. Histological findings showed mast cell hyperplasia (100%), superficial perivascular infiltrate of lymphocytes (94%), and superficial edema (47%) consistent with capillary leak. CONCLUSIONS: Various dermatological signs can be encountered during COVID-19. A macular rash was the most frequent. All cutaneous features could be related to a vascular leak process.

Efficacy of cefoxitin for the treatment of urinary tract infection due to extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates.

INTRODUCTION: Cefoxitin has a good in vitro activity and stability in resistance to hydrolysis by extended-spectrum beta-lactamases and is a good candidate for the treatment of urinary tract infection. However, data are scarce regarding its use in clinical practice. METHODS: We conducted a retrospective study from September 2014 to November 2017, in a tertiary care hospital in Garches (France). We gathered all prescriptions of cefoxitin for urinary tract infection due to extended-spectrum beta-lactamase isolates. We compared the clinical outcomes between Escherichia coli and Klebsiella pneumoniae extended-spectrum-beta-lactamase-producing isolates after a 90-day follow-up. When available, we assessed whether cefoxitin-based regimen was associated with an emergence of resistance. RESULTS: The treatment of 31 patients with a mean age of 60 ± 18 years was analyzed. We observed a clinical cure of 96.7% (n = 30/31) at day 30 and of 81.2% (n = 13/16) and 85.7% (12/14) at day 90 for extended-spectrum beta-lactamase Escherichia coli and Klebsiella pneumoniae isolates, respectively (p = 0.72). No adverse events were reported. One patient who relapsed carried a Klebsiella pneumoniae isolate that became intermediate to cefoxitin in the follow-up. CONCLUSION: In a period of major threat with a continuous increase of extended-spectrum beta-lactamase obliging to a policy of carbapenem-sparing regimens, it seems detrimental to deprive physicians of using cefoxitin for extended-spectrum beta-lactamase Enterobacteriaceae for the treatment of urinary tract infection while our data show its efficacy.

Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs).

INTRODUCTION: Cotrimoxazole (Sulfamethoxazole-Trimethoprim, SXT) has interesting characteristics for the treatment of bone and joint infection (BJI): a broad spectrum of activity with adequate bone diffusion and oral and intravenous formulations. However, its efficacy and safety in BJIs are poorly documented and its use remains limited. METHODS: We conducted a retrospective study in 2 reference centers for BJIs from 2013 to 2018 among patients treated with SXT for a BJI. Data were collected from patient's medical charts. Outcomes and adverse events were evaluated at day (D)7, D45 and D90. RESULTS: We analyzed 51 patients with a mean age of 60 ± 20 (SD) years of which 76% presented with an orthopedic device infection (ODI). Gram-negative bacilli (GNB) were involved in 47% of BJIs (n = 24). Moreover, they were often polymicrobial infections (41%). Doses of SXT ranged from 800/160mg bid (61%; n = 31) to 800/160mg tid (39%; n = 20). Median SXT treatment duration was 45 days (IQR 40-45). SXT was part of a dual therapy in 84% of patients (n = 43), associated mainly with fluoroquinolones (n = 17) or rifampicin (n = 14). Outcome was favorable at D7 in 98% (n = 50), at D45 in 88.2% (n = 45) and at D90 in 78.4% (n = 40). The second agent combined with SXT was not an independent factor of favorable outcome (p = 0.97). Adverse events were reported in 8% (n = 4) of patients, with a median of 21 days (IQR 20-30) from SXT initiation and led to discontinuation (n = 3). CONCLUSION: SXT appears to be effective for treatment of BJIs as a salvage therapy, even in GNB or polymicrobial infection, including ODI. Further data are needed to confirm SXT efficacy as an alternative oral regimen in BJIs.

Germs of thrones - spontaneous decolonization of Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) in Western Europe: is this myth or reality?

Background: In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital's hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods: Retrospective multicenter study over 2 years (2015-2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient's follow-up. We also evaluated patient care considering isolation precautions. Results: We included 125 patients, aged 63+/-19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3).Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up.Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0-974).We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15-300). Conclusions: Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies.