Pseudomonal Diabetic Foot Infections: Vive la Différence?

Objective To assess the outcomes of diabetic foot infections (DFIs) due to Pseudomonas aeruginosa. Patients and Methods From April 24, 2013 to July 31, 2016, we analyzed data from patients prospectively enrolled in our clinical pathway of DFIs, comparing those with infection due to Pseudomonas with those without infection due to Pseudomonas. Results Overall, we assessed 1018 cases of DFIs: 392 with osteomyelitis and 626 with only soft tissue infections. The prevalence of P aeruginosa in deep wound cultures was 10% (104/1018); of the 1018 cultures, 22 were monomicrobial, 82 were polymicrobial, and 46 were with osteomyelitis. Overall, the patients were treated with a median of 1 surgical debridement and a total of 20 days of antibiotic therapy. In a comparison of crude groups, the proportion of clinical failures was significantly higher with Pseudomonas than with other pathogens (36/104 [35%] vs 218/914 [24%], respectively; P=.02). A multivariate analysis showed that pseudomonal DFIs did not recur more often than nonpseudomonal DFIs (hazard ratio, 1.0; 95% confidence interval, 0.6-1.7). Among the 104 cases of pseudomonal DFIs, there was no association between failure of treatment and the total duration of antibiotic therapy, duration of intravenous therapy, duration of combined antibiotic therapy with more than 1 agent, or duration of oral (fluoroquinolone) therapy. Among 15 cases of pseudomonal recurrence, 2 (13%) developed resistance to the antibiotic agent used for the index episode. Conclusion For DFIs caused by P aeruginosa, other than choosing an antibiotic agent that is active against the organism, it does not appear necessary to treat with a different therapeutic regimen compared with the treatment of nonpseudomonal DFIs. There is no difference

Duration of antibiotic treatment for Gram-negative bacteremia - Systematic review and individual participant data (IPD) meta-analysis

Background: We aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups. Methods: Individual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence.Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment. Findings: Three RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73-1.58; 30-day mortality: 1.08, 0.62-1.91). Relapse (1.00, 0.50-1.97); length of hospital stay (P = 0.78); readmission (0.96, 0.80-1.22); and infection complications (local: 1.62 0.76-3.47; distant: 2.00, 0.18-22.08), were without significant difference, and so were adverse events or resistance emergence.No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection. Interpretation: For patients hemodynamically stable and afebrile at 48 h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation. Funding: There was no funding source for this study

Population Pharmacokinetics of Imipenem in Critically Ill Patients: A Parametric and Nonparametric Model Converge on CKD-EPI Estimated Glomerular Filtration Rate as an Impactful Covariate

Background: Population pharmacokinetic (popPK) models for antibiotics are used to improve dosing strategies and individualize dosing by therapeutic drug monitoring. Little is known about the differences in results of parametric versus nonparametric popPK models and their potential consequences in clinical practice. We developed both parametric and nonparametric models of imipenem using data from critically ill patients and compared their results. Methods: Twenty-six critically ill patients treated with intravenous imipenem/cilastatin were included in this study. Median estimated glomerular filtration rate (eGFR) measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 116 mL/min/1.73 m2 (interquartile range 104–124) at inclusion. The usual dosing regimen was 500 mg/500 mg four times daily. On average, five imipenem levels per patient (138 levels in total) were drawn as peak, intermediate, and trough levels. Imipenem concentration-time profiles were analyzed using parametric (NONMEM 7.2) and nonparametric (Pmetrics 1.5.2) popPK software. Results: For both methods, data were best described by a model with two distribution compartments and the CKD-EPI eGFR equation unadjusted for body surface area as a covariate on the elimination rate constant (Ke). The parametric population parameter estimates were Ke 0.637 h−1 (between-subject variability [BSV]: 19.0% coefficient of variation [CV]) and central distribution volume (Vc) 29.6 L (without BSV). The nonparametric values were Ke 0.681 h−1 (34.0% CV) and Vc 31.1 L (42.6% CV). Conclusions: Both models described imipenem popPK well; the parameter estimates were comparable and the included covariate was identical. However, estimated BSV was higher in the nonparametric model. This may have consequences for estimated exposure during dosing simulations and should be further investigated in simulation studies

Staphylocoque doré méticilline résistant (MRSA) : Prévention et lutte contre ce pathogène

Staphylococcus aureus is a bacterium that can cause blood infections that can have a community or hospital origin. Among people infected with S.aureus, about 20-25% is healthy adults that carry the pathogen on their bodies, without suffering any symptom (they are said "colonized"). Although asymptomatic and often benign, colonization with S. aureus involves a risk of secondary infection and represents a serious risk of transmission to a third party. In hospitals, the risk of infection and transmission appears to be unusually high for methicillinresistant S. aureus (MRSA) and complications can be very severe. Prevention and the fight against MRSA is a major public health concern. The United Nations recently engaged in this struggle by creating the "Global Action Plan on Antimicrobial Resistance". This work is about three different studies in the prevention and control of this pathogen.Le Staphylocoque aureus (S. aureus) est une bactérie pouvant causer des infections d’origine communautaire ou hospitalière. En plus des personnes pouvant être infectées par S. aureus, de nombreux individus environ 20-25% parmi les adultes en bonne santé, portent ce pathogène sur leurs corps (ils sont dits "colonisés"). Bien qu’asymptomatique et souvent bénigne, la colonisation à S. aureus peut rarement impliquer un risque d’infection secondaire grave mais représente un risque d’être transmise à une tierce personne. A l’hôpital, le risque d’infection et de transmission apparaît comme étant particulièrement haut pour la souche de S. aureus résistante à la méticilline (SARM). La prévention et la lutte contre le SARM est un problème de santé publique important. Les Nation Unis se sont récemment engagés dans cette lutte en créant le"Global Action Plan on Antimicrobial Resistance". Ce travail de thèse traite de trois différentes études dans la cadre de la prévention et du contrôle de ce pathogène

Comparative Genomics of Community-Associated Methicillin-Resistant Staphylococcus aureus Shows the Emergence of Clone ST8-USA300 in Geneva, Switzerland

Background.  Previous investigations of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates have revealed a wide diversity of genetic backgrounds, with only sporadic occurrence of ST8-USA300, in Geneva, Switzerland. We conducted a molecular epidemiologic analysis to identify the origin of a sudden increase of ST8 PVL-positive isolates in Geneva during 2013. Methods.  On the basis of prospective CA-MRSA surveillance, we collected colonizing and infecting ST8-USA300 isolates and compared them to non-ST8 CA-MRSA isolates. Whole-genome sequencing (WGS) was performed for each isolate of this collection, and discriminating molecular features were linked to patient data. Results.  In 2013, 22 isolates with the ST8-USA300 profile were identified among 46 cases of CA-MRSA. WGS revealed 2 groups of strains that differed by the type of the SCCmec IV element encoded and whether they harbored an arginine catabolism mobile element (ACME) locus. ACME-negative strains were mainly isolated from patients traveling in or originating from South America. Single-nucleotide polymorphism positions in isolate groups were used to infer their common ancestor, determine their geographical origin, and trace their relatedness. Conclusions.  WGS allowed the identification of transmission events and revealed that the increased prevalence of USA300 CA-MRSA isolates resulted from multiple importation events from the Americas but not from local clonal expansion of a successful clone

Remission in diabetic foot infections: Duration of antibiotic therapy and other possible associated factors

AIM To determine the most appropriate duration of antibiotic therapy for diabetic foot infections (DFIs). METHODS Using a clinical pathway for adult patients with DFIs (retrospective cohort analysis), we created a cluster-controlled Cox regression model to assess factors related to remission of infection, emphasizing antibiotic-related variables. We excluded total amputations as a result of DFI and DFI episodes with a follow-up time of <2 months. RESULTS Among 1018 DFI episodes in 482 patients, we identified 392 episodes of osteomyelitis, 626 soft tissue infections, 246 large abscesses, 322 episodes of cellulitis and 335 episodes of necrosis; 313 cases involved revascularization. Patients underwent surgical debridement for 824 episodes (81%), of which 596 (59%) required amputation. The median total duration of antibiotic therapy was 20 days. After a median follow-up of 3 years, 251 of the episodes (24.7%) were followed by ≥1 additional episode(s). Comparing patients with and without additional episodes, risk of recurrence was lower in those who underwent amputation, had type 1 diabetes, or underwent revascularization. On multivariate analysis including the entire study population, risk of remission was inversely associated with type 1 diabetes (hazard ratio [HR] 0.3, 95% confidence interval [CI] 0.2-0.6). Neither duration of antibiotic therapy nor parenteral treatment affected risk of recurrence (HR 1.0, 95% CI 0.99-1.01 for both). Similarly, neither >3 weeks versus 1 week versus 3 weeks overall and 0.6 (95% CI 0.2-1.3) for osteomyelitis cases only. Plotting of duration of antibiotic therapy failed to identify any optimal threshold for preventing recurrences. CONCLUSIONS Our analysis found no threshold for the optimal duration or route of administration of antibiotic therapy to prevent recurrences of DFI. These limited data might support possibly shorter treatment duration for patients with DFI

Patient and Proxy Recall After Providing Written or Oral Informed Consent to Participate in an Interventional Trial

This cohort study assesses recall rates among patients and their proxies who consented to participate in a randomized clinical trial

Impact of restricting procalcitonin measurements in a Swiss tertiary-care hospital on antibiotic use, clinical outcomes, and costs: An interrupted time-series analysis

We evaluated the impact of a restriction of procalcitonin measurements on antibiotic use, length of stay, mortality, and cost in a Swiss tertiary-care hospital using interrupted time-series analysis. There was no significant change in level or slope for rates of antibiotic consumption, and costs decreased considerably, by ~54,488 CHF (US$55,714) per month