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.

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.

Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.

UNLABELLED: Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. PATIENTS AND METHODS: Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients' total body weight adjusted for renal clearance. RESULTS: A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean serum vancomycin concentrations were not significantly different (19.9 ± 11.2 mg/L in period 1 vs 18.9 ± 6.0 mg/L in period 2, P=0.64). In the final generalized estimating equations model, serum vancomycin concentrations correlated statistically with a positive coefficient for age (P<0.001) and with negative coefficients for male sex (P=0.001) and hemoglobin level (P=0.021). CONCLUSION: Serum vancomycin concentrations measured 48 hours after the start of an empirical treatment were not influenced by the nature of the generic product but correlated with age, sex and hemoglobin level in AML patients.

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.

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients.

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ≥5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ≥500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ≥500 and 350-499/mm3, respectively). In patients with a baseline HIV viral load ≤3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ≥500 and 350-499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load 5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ≥350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.

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.

High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.

BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients. RESULTS: As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months. CONCLUSIONS: In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.

[Presumptive bacterial meningitis in adults: initial antimicrobial therapy]. / Méningites présumées bactériennes communautaires de l'adulte : antibiothérapie initiale.

CSF sterilization should be obtained very rapidly to reduce both mortality and morbidity due to bacterial meningitis. Thus, antibiotic treatment should be adapted to the suspected bacterium and administered as early as possible at high dosage with - if necessary - a loading dose and continuous perfusion. The rates of abnormal susceptibility to penicillin of Streptococcus pneumoniae, Neisseria meningitis and Haemophilus influenzae are 37%, 30% and 12% respectively. Thus, ceftriaxone or cefotaxim must be used as empirical treatment. Listeria monocytogenes remains fully susceptible to aminopenicillin, so, the combination aminopenicillin and aminoglycoside is the first-line treatment. Antibiotic resistance, allergy or contra-indications, are in fact rare but in these cases, antibiotic combinations are often needed. The latter are more or less complex and clinically validated; they include molecules such as vancomycine, fosfomycin, fluoroquinolone or linezolid.

[Incidence, prevalence and risk factors for a first infectious complication on a totally implantable venous-access port]. / Incidence, prévalence et facteurs de risque de survenue d'une première complication infectieuse sur chambres à cathéter implantables.

BACKGROUND: Totally implantable venous-access ports (TIVAP) should present less risk of complications than central venous catheters over a long time period. AIMS: Firstly, the study's objective was to assess the prevalence and incidence of a first infectious complication on a TIVAP and secondly, to assess the risk factors associated with this first infection. METHODS: The authors made a longitudinal historical cohort study of patients with a TIVAP in 2003, in the Dijon University Hospital. RESULTS: Two hundred and nineteen patients (sex-ratio 1.9) were included, with a total follow-up of 92,773 patients-days. Ninety percent of the TIVAP were used for chemotherapy, 5% for antibiotic drug administration, 2% for parenteral nutrition and 3% for other reasons (recurrent blood transfusions, etc.). Overall, 34 (16.3%) out of 209patients presented with at least one infectious complication, with an incidence rate of 0.37infection/1,000patients-days. The 5-year cumulative probability to be free of infectious complication was only 62.8%. In multivariate analysis, only underlying hematological neoplasia (by contrast with solid tumors) was significantly associated to a higher risk of infectious complication. CONCLUSIONS: The infectious risk linked to the use of TIVAP is significant, higher in case of underlying hematological neoplasia and during the first months of use.

[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.

Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment.

OBJECTIVE: To assess the incidence and risk factors for severe liver toxicity in human immunodeficiency virus (HIV) infected patients on anti-tuberculosis treatment and the impact of patients' characteristics and concomitant medications instituted during the first week of antituberculosis treatment. METHODS: HIV-infected patients referred to six French hospitals between 1 January 1992 and 31 December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity was studied during the first 2 months of TB treatment. RESULTS: During the 12 years of the study period, 144 patients were enrolled. Severe liver toxicity developed in 15 (10.7%). The median time to development of liver toxicity was 14 days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4 cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole (P = 0.0005) were associated with liver toxicity. In the multivariate analysis, independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008). CONCLUSION: Severe liver toxicity is frequent, and occurs early in the course of anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored during the first month of treatment, especially in patients with high baseline ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti-tuberculosis drugs concomitantly, although this needs to be confirmed and further investigated.

[Pulmonary abscess and Pyoderma gangrenosum]. / Abcès pulmonaire et Pyoderma gangrenosum.

INTRODUCTION: Pyoderma gangrenosum is the ulcerative form of neutrophilic dermatoses. The most frequent extracutaneous localizations are the lungs, joints, and digestive tract. CASE RECORD: We report a case of Pyoderma gangrenosum, which presented first as an aseptic lung abscess. The first cutaneous lesions occurred 9 months later, with skin ulcerations on the thorax and on surgical scars. The histological diagnosis was made on skin biopsies. There was no associated abnormality except for IgA monoclonal gammapathy. Clinical improvement was noted with immunosuppressive treatment. DISCUSSION: This infrequent case report underlines that lung abscesses may be of non-infectious origin, that in Pyoderma gangrenosum, skin lesions may be come several months after extracutaneous manifestations, among which lungs abcesses are the most frequent.

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.