Efficacy of ceftaroline and rifampin, alone or combined, in a rat model of methicillin-resistant Staphylococcus epidermidis osteomyelitis without implant.

IMPORTANCE: Methicillin-resistant Staphylococcus epidermidis (MRSE) contributes to a high percentage of orthopedic infections, and their treatment represents a huge challenge. The present study aimed to evaluate the efficacy of ceftaroline alone or combined with rifampin in a rat MRSE osteomyelitis model and the bone penetration of ceftaroline. A ceftaroline monotherapy showed a significant bacterial reduction in infected bones after a 7-day period of treatment. The combination ceftaroline plus rifampin leveraged rifampin's bactericidal activity, shortening the duration of positive culture in infected animals. These results suggest that ceftaroline and rifampin combination therapy could represent a valuable therapeutic option for human MRSE osteomyelitis and deserves further preclinical and clinical evaluation.

Antibiotic therapy in the emergency room: Optimal prescription is indeed the best.

INTRODUCTION: Emergency departments (ED) are pivotal for antibiotic prescription, of which the appropriateness and consequences have rarely been assessed. METHODS: A retrospective study included patients referred to the ED and hospitalized with an advocated diagnosis of infection. Day-0 (ED initial prescription) and day-2 (reevaluation) antibiotic therapies were graded as optimal (if fully following the guidelines in terms of molecule, dose, and route of administration), adapted (if the prescribed molecule was microbiologically active but not recommended as first-line treatment, or in case of a wrong dose), or inadequate (other situations). The primary endpoint was onset of an unfavorable event (death, transfer to intensive care unit, or re-hospitalization). Prognosis factors associated with survival without unfavorable event were assessed by multivariate analysis. RESULTS: We included 484 patients. Optimal, adapted, and inadequate initial prescriptions concerned 328 (67.8 %), 110 (22.7 %) and 46 (9.5 %) patients respectively. Compared with an optimal prescription, an initial adapted prescription was associated with a poorer prognosis (HR = 1.95, CI95% [1.18-3.22]; p = 0.01). Reevaluation was performed in 436 (90.1 %) patients. After reevaluation, optimal, adapted, and inadequate prescriptions concerned 326 (74.8 %), 64 (14.7 %), and 46 (10.5 %) patients respectively. After reevaluation, and as compared with optimal prescription, inadequate prescription was significantly associated with unfavorable events (HR = 3.52, CI95% [1.42-8.72]; p = 0.003). CONCLUSION: Antibiotics are frequently prescribed in EDs. Antibiotic prescription has got to be optimal, and not simply adapted, so as to be associated with significant clinical benefit.

Is there a need to widely prescribe antibiotics in patients hospitalized with COVID-19?

BACKGROUND: Debate continues regarding the usefulness and benefits of wide prescription of antibiotics in patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: All patients hospitalized in the Infectious Diseases Department, Dijon University Hospital, Dijon, France between 27 February and 30 April 2020 with confirmed COVID-19 were included in this study. Clinical, biological and radiological data were collected, as well as treatment and outcome data. An unfavourable outcome was defined as death or transfer to the intensive care unit. Patient characteristics and outcomes were compared between patients who did and did not receive antibiotic therapy using propensity score matching. FINDINGS: Among the 222 patients included, 174 (78%) received antibiotic therapy. The univariate analysis showed that patients who received antibiotic therapy were significantly older, frailer and had more severe presentation at admission compared with patients who did not receive antibiotic therapy. Unfavourable outcomes were more common in patients who received antibiotic therapy [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.07-8.11; P = 0.04]. Multi-variate analysis and propensity score matching indicated that antibiotic therapy was not significantly associated with outcome (HR 1.612, 95% CI 0.562-4.629; P = 0.37). CONCLUSION: Antibiotics were frequently prescribed in this study and this was associated with more severe presentation at admission. However, antibiotic therapy was not associated with outcome, even after adjustment. In line with recent publications, such data support the need to streamline antibiotic therapy in patients with COVID-19.

Comparative review of imipenem/cilastatin versus meropenem.

INTRODUCTION: Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services. OBJECTIVE: We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike. METHOD: Review of the literature by querying the MEDLINE network. RESULTS: Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin. CONCLUSION: Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.

Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant.

We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log10 CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log10 CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.

Efficacy of Bacteriophages in a Staphylococcus aureus Nondiabetic or Diabetic Foot Infection Murine Model.

This study investigated the in vivo efficacy of three bacteriophages combined compared with linezolid in two mouse models (nondiabetic and diabetic) of Staphylococcus aureus foot infection. In both models, a single injection of bacteriophages in the hindpaw showed significant antibacterial efficacy. Linezolid was as effective as bacteriophages in nondiabetic animals but ineffective in diabetic animals. These findings further support preclinical and clinical studies for the development of phage therapy.

[Influenza infection: An update for clinicians]. / La grippe : mise au point pour les cliniciens.

Lower respiratory infections remain the deadliest communicable disease in the world. Influenza infections are particularly involved, whether intrinsically, or more frequently, by promoting bacterial infections and superinfections. The flu is also responsible for the decompensation of many comorbidities and could lead to some myocardial infarction and stroke. The effect of antiviral therapies is limited but preventives measures, such as vaccination, remain a major public health issue. The flu is a major challenge at all levels and all times, from vaccine prevention, to the recognition of atypical forms, and the early management of bacterial complications.

Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients.

OBJECTIVE: To assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients. PATIENTS AND METHODS: Patients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations. RESULTS: Of the 263 patients who participated in the 2010 study, 198 were included in the 2012 study. Hypovitaminosis D was observed in 47% (36/77) of participants supplemented as per appropriate guidelines, in 78% (75/97) of transiently or incompletely supplemented participants, and in 71% (17/24) of non-supplemented participants (mainly because vitamin D levels in 2010 were normal). No significant correlation between vitamin D supplementation and the 2-year inflammation outcome (IL-6 and hsCRP) or C-terminal telopeptide levels was observed. However, a decrease in IL6 levels over the 2 years significantly correlated with reaching a normal vitamin D level (OR=0.89 per+1pg/mL IL6 increase, 95% CI=0.81-0.97, P=0.015). CONCLUSIONS: Vitamin D supplementation decreases the risk of hypovitaminosis D but does not decrease the risk of inflammation nor bone turnover, unless normal 25-OH vitamin D levels are reached.

Update on childhood and adult infectious tracheitis.

The trachea is a pivotal organ of the respiratory tract. Rather than a genuine anatomic border, it acts as a crossroad in all respiratory infectious processes. Even though not strictly limited to the trachea, infections such as laryngotracheitis and tracheobronchitis are frequently diagnosed in children, in particular during the winter season. Infectious tracheitis etiologies are diverse and the distinction between viral and bacterial origins, albeit difficult, remains relevant considering the substantial differences in terms of gravity and therapeutic management. This literature review summarizes the microbiological and clinical aspects of community-acquired and nosocomial tracheitis in adults and children, as well as the adequate diagnostic and therapeutic approaches. It also highlights the emergence of fungal tracheitis in immunocompromised patients, of ventilator-associated tracheitis in intensive care medicine, and beyond all that the potential short and long-term consequences of tracheitis.

Association between Pseudomonas aeruginosa positive water samples and healthcare-associated cases: nine-year study at one university hospital.

OBJECTIVE: To study the association between the results of water samples and Pseudomonas aeruginosa healthcare-associated cases in a French university hospital. METHODS: Generalized Estimating Equations were used on complete case and imputed datasets. The spatial unit was the building and the time unit was the quarter. RESULTS: For the period 2004-2013, 2932 water samples were studied; 17% were positive for P. aeruginosa. A higher incidence of P. aeruginosa cases was associated with a higher proportion of positive water samples (P=0.056 in complete case analysis and P=0.031 with the imputed dataset). The association was no longer observed when haematology and intensive care units were excluded, but was significant in analyses of data concerning intensive care units alone (P<0.001). CONCLUSION: This study suggests that water outlet contamination in hospitals can lead to an increase in healthcare-associated P. aeruginosa cases in wards dealing with susceptible patients, but does not play a significant role in other wards.

Detection of temporal clusters of health care-associated infections or colonizations with Pseudomonas aeruginosa.

We investigated temporal clusters of Pseudomonas aeruginosa cases between 2005 and 2014 in 1 French university hospital, overall and by ward, using the Kulldorff method. Clusters of positive water samples were also investigated at the whole hospital level. Our results suggest that water outlets are not closely involved in the occurrence of clusters of P aeruginosa cases.

Abdominal tuberculosis in a low prevalence country.

OBJECTIVE: Abdominal tuberculosis is a rare disease. The clinical and radiological manifestations are non-specific and the diagnosis is difficult. Our objective was to describe the characteristics and treatment of patients presenting with abdominal tuberculosis in a low-incidence country. PATIENTS AND METHODS: We reviewed the clinical, diagnostic, treatment, and outcome features of patients presenting with abdominal tuberculosis diagnosed by bacteriological and/or histological results and managed in five French university hospitals from January 2000 to December 2009. RESULTS: We included 21 patients. The mean diagnostic delay was 13 months. Twelve patients (57%) came from a low-incidence area and only two had a known immunosuppressed condition. Eighteen patients (86%) presented with abdominal symptoms. The main organs involved were the peritoneum (n=14, 66%), the mesenteric lymph nodes (n=13, 62%), and the bowel (n=7, 33%). Sixteen patients (76%) underwent surgery, including two in an emergency setting. Seventeen patients (81%) received six months or more of anti-tuberculosis treatment. Finally, 16 patients (76%) had a positive outcome. CONCLUSION: New diagnostic procedures, and especially molecular biology, may help diagnose unusual clinical presentations of tuberculosis. Invasive procedures are frequently necessary to obtain samples but also for the treatment of digestive involvement.

Impact of microbiological samples in the hospital management of community-acquired, nursing home-acquired and hospital-acquired pneumonia in older patients.

We investigated the positivity rate, the detection rates for non-covered pathogens and the therapeutic impact of microbiological samples (MS) in community-acquired pneumonia (CAP), nursing home-acquired pneumonia (NHAP) and hospital-acquired pneumonia (HAP) in elderly hospitalised patients. Patients aged 75 years and over with pneumonia and hospitalised between 1/1/2013 and 30/6/2013 in the departments of medicine (5) and intensive care (1) of our university hospital were included. Microbiological findings, intra-hospital mortality and one-year mortality were recorded. Among the 217 patients included, there were 138 CAP, 56 NHAP and 23 HAP. MS were performed in 89.9, 91.1 and 95.6 % of CAP, NHAP and HAP, respectively. Microbiological diagnosis was made for 29, 11.8 and 27.3 % of patients for CAP, NHAP and HAP, respectively (p = 0.05). Non-covered pathogens were detected for 8 % of CAP, 2 % of NHAP and 13.6 % of HAP (p = 0.1). The antimicrobial spectrum was significantly more frequently reduced when the MS were positive (46.7 % vs. 10.8 % when MS were negative, p = 10(-7)). The MS positivity rate was significantly lower in NHAP than in CAP and HAP. MS revealed non-covered pathogens in only 2 % of NHAP. These results show the poor efficiency and weak clinical impact of MS in the management of pneumonia in hospitalised older patients and suggest that their use should be rationalised.

Information concerning multidrug-resistant bacterial colonization or infection in the medical transfer letter.

OBJECTIVES: The aim of this study was to evaluate the proportion of transfer letters that contained information relative to infection or colonization by multidrug-resistant (MDR) bacteria and factors associated with the presence of that information. PATIENTS AND METHODS: Patients for whom at least one of these selected MDR bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum ß-lactamase-producing Enterobacteriaceae, or MDR Pseudomonas aeruginosa) was isolated during their hospitalization and who were transferred to another health care facility between 2009 and 2012 were included. Information of the MDR bacterium and the mention of isolation precautions were evaluated in the electronic medical record. RESULTS: Information (mention of MDR bacterium or isolation precaution) was present in 57% [52; 65] of records. Full information (genus and species, concept of MDR bacterium and mention of isolation precaution) was found in 20% [16; 25]. The presence of a dedicated item in the standard medical discharge letter was associated with more frequent information. Less information was retrieved with P. aeruginosa cases than with the other 2 MDR bacteria. CONCLUSION: The presence of the information has improved, but it is still insufficiently reported. Measures to improve information are needed. Indeed, information on MDR bacterial colonization or infection is the first step for isolation precautions. An item could be added to all standard medical discharge letters. An item could also be added to the indicators used to assess quality and safety in healthcare facilities.