A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections: are carbapenem alternatives achievable in daily practice?

Objectives: To avoid the use of carbapenems, alternatives such as cephamycin, piperacillin–tazobactam, and others are suggested for the treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections. The aim of this study was to evaluate the frequency and the feasibility of antimicrobial de-escalation for ESBL-PE-related infections. Methods: A prospective observational, bi centric cohort study was conducted. All patients with ESBL-PE infections were included. De-escalation was systematically suggested if patients were clinically stable and the isolate was susceptible to possible alternatives. Results: Seventy-nine patients were included: 36 (45.6%) were children, 27 (34.1%) were hospitalized in intensive care units, and 37 (47%) were immunocompromised. Urinary tract infections, pneumonia, and catheter-related bloodstream infections accounted for 45.6%, 19%, and 10%, respectively, of the cohort. Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were the three most frequent causative organisms isolated. On day 5, 47 (59.2%) of the patients were still receiving carbapenems. Antimicrobial resistance (44.7%), infection relapse (26.9%), and clinical instability (19.2%) were the most important reasons for not prescribing alternatives. E. coli-related infections appeared to be a protective factor against maintaining the carbapenem prescription (odds ratio 0.11, 95% confidence interval 0.041–0.324; p = 0.0013). Conclusions: In clinical practice, less than 50% of patients with ESBL-PE-related infections were de-escalated after empirical treatment with carbapenems

Potential impact of real-time processing and rapid susceptibility testing of blood samples in Gram-negative bloodstream infections in intensive care patients

International audienceIntroduction: Timely and appropriate therapy is critical in patients with Gram-negative bloodstream infections (GNBSI). Most bacteriology laboratories process blood specimen in the daytime, during laboratory operating hours, and use conventional culture for antimicrobial susceptibility testing (AST). We simulated the potential impact of real-time processing and rapid AST (7 hours) on early adaptation of the antibiotic regimen in intensive care unit (ICU) patients with GNBSI.Methods: All GNBSI episodes occurring in the ICUs of 2 hospitals in Paris were included. Data were collected. For each episode of bacteremia, we simulated the impact of three strategies: (1) Real-time processing coupled with conventional techniques (Gram stain and standard AST); (2) Standard processing coupled with rapid AST; and (3) Real-time processing coupled with rapid AST.Results: We included 109 episodes in 98 patients. Forty-two patients (48%) died during ICU stay. AST results led to a change of the antibiotic regimen in 66 (61%) episodes, mainly de-escalation (54/109, 55%). In standard care, median time from sample collection to definitive AST result was 65.9 hours (±26.7). The three strategies would have reduced time-to-result by 9.2 hours (±7.1), 30.8 hours (±19.7) and 40.0 hours (±20.6) respectively. Compared to standard care, strategies 1, 2 and 3 would have avoided 20, 69 and 90 patient-days of broad-spectrum antibiotics respectively.Conclusion: In addition to real-time processing of blood samples, rapid AST would be the most effective strategy to shorten time-to-result in critical patients with GNBSI

Prognosis of prosthetic valve infective endocarditis due to Streptococcus spp., a retrospective multi-site study to assess the impact of antibiotic treatment duration

Purpose: The duration of antibiotic treatment for prosthetic valve endocarditis caused by Streptococcus spp. is largely based on clinical observations and expert opinion rather than empirical studies. Here we assess the impact of a shorter antibiotic duration. Objectives: To assess the impact of antibiotic treatment duration for streptococcal prosthetic valve endocarditis on 12-month mortality as well as subsequent morbidity resulting in additional cardiac surgical interventions, and rates of relapse and reinfection. Methods: This retrospective multisite (N= 3) study examines two decades of data on patients with streptococcal prosthetic valve endocarditis receiving either 4 or 6 weeks of antibiotics. Overall mortality, relapse, and reinfection rates were also assessed for the entire available follow-up period. Results: The sample includes 121 patients (median age 72 years, IQR [53; 81]). The majority (74%, 89/121) received a ß-lactam antibiotic combined with aminoglycoside in 74% (89/121, median bi-therapy 5 days [1; 14]). Twenty-eight patients underwent surgery guided by ESC-guidelines (23%). The 12-month mortality rate was not significantly affected by antibiotic duration (4/40, 10% in the 4-week group vs 3/81, 3.7% in the 6-week group, p=0.34) or aminoglycoside usage (p=0.1). Similarly, there were no significant differences between the 2 treatment groups for secondary surgical procedures (7/40 vs 21/81, p=0.42), relapse or reinfection (1/40 vs 2/81 and 2/40 vs 5/81 respectively). Conclusions: Our study found no increased adverse outcomes associated with a 4-week antibiotic duration compared to the recommended 6-week regimen. Further randomized trials are needed to ascertain the optimal duration of treatment for streptococcal endocarditis

Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review

International audienceThe burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of β-lactamases or by deregulation of natural genetically-encoded β-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC β-lactamases. AmpC can be overproduced as a response to β-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infectio