Distribution, Consequences, and Determinants of Time to Antibiotics in Children With Community-Onset Severe Bacterial Infection: A Secondary Analysis of a Prospective Population-Based Study.

OBJECTIVES: To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs). DESIGN: Secondary analysis of the available data from a prospective population-based study from 2009 to 2014. SETTING: An administrative area in western France accounting for 13% of the national pediatric population. PATIENTS: All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine. CONCLUSIONS: For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs.

Interleukin-33 Deficiency Exacerbates Bone Loss Associated with Porphyromonas Gingivalis-Induced Experimental Periodontitis in Female Mice.

BACKGROUND/AIMS: Interleukin 33 (IL-33) plays a significant role in immunity but its role in bone physiology and periodontitis needs to be further investigated. The aim of this study was to decipher the contribution of IL-33 to bone homeostasis under physiological conditions, and to alveolar bone loss associated with experimental periodontitis (EP) in IL-33 knockout (KO) mice and their wildtype (WT) littermates. METHODS: The bone phenotype of IL-33 KO mice was studied in the maxilla, femur, and fifth lumbar vertebra by micro-computed tomography (micro-CT). EP was induced by a ligature soaked with the periopathogen Porphyromonas gingivalis (Pg) around a maxillary molar. Alveolar bone loss was quantified by micro-CT. The resorption parameters were assessed via toluidine blue staining on maxillary sections. In vitro osteoclastic differentiation assays using bone marrow cells were performed with or without lipopolysaccharide from Pg (LPS-Pg). RESULTS: First, we showed that under physiological conditions, IL-33 deficiency increased the trabecular bone volume/total volume ratio (BV/TV) of the maxillary bone in male and female mice, but not in the femur and fifth lumbar vertebra, suggesting an osteoprotective role for IL-33 in a site-dependent manner. The severity of EP induced by Pg-soaked ligature was increased in IL-33 KO mice but in female mice only, through an increase in the number of osteoclasts. Moreover, osteoclastic differentiation from bone marrow osteoclast progenitors in IL-33-deficient female mice is enhanced in the presence of LPS-Pg. CONCLUSION: Taken together, our data demonstrate that IL-33 plays a sex-dependent osteoprotective role both under physiological conditions and in EP with Pg.

Persistence of a multidrug-resistant worldwide-disseminated methicillin-resistant Staphylococcus epidermidis clone harbouring the cfr linezolid resistance gene in a French hospital with evidence of interspecies transfer to several Staphylococcus aureus lineages.

BACKGROUND: Resistance to linezolid has become a worldwide concern since it is one of the last-resort antibiotics to treat multidrug-resistant staphylococcal and enterococcal infections. OBJECTIVES: We investigated staphylococcal infections caused by 16 cfr-positive linezolid-resistant Staphylococcus epidermidis and Staphylococcus aureus isolates in a French university hospital from 2015 to 2018. METHODS: Antimicrobial susceptibility of isolates was tested by broth microdilution and gradient strips. Genetic determinants of linezolid resistance (including cfr gene and 23S rRNA mutations) were assessed by PCR and WGS; the latter was also used to characterize the cfr-carrying plasmids in S. epidermidis and S. aureus, and to explore the clonal relationship of isolates. RESULTS: All linezolid-resistant staphylococcal isolates harboured the same cfr-carrying plasmid, sharing 99% identity with the previously described pSA737. The three S. aureus isolates belonged to different STs (ST8, ST72, ST2416); the 13 methicillin-resistant S. epidermidis (MRSE) belonged to ST2 and harboured both cfr and mutations in genes encoding 23S rRNA and ribosomal proteins. Phylogenetic analysis grouped the MRSE isolates into two clusters, one of which (n = 12 isolates) belonged to the recently reported multidrug-resistant worldwide-disseminated S. epidermidis lineages. CONCLUSIONS: The results presented herein highlight the persistence and efficient spread of a cfr-carrying plasmid in a hospital related both to the dissemination of a multidrug-resistant S. epidermidis clone and the in vivo interspecies transfer of cfr between S. epidermidis and S. aureus. The emergence of linezolid-resistant strains should be closely monitored, and the mechanisms involved systematically explored in order to limit the spread of plasmid-mediated resistance.

Efficacy of Nanoencapsulated Daptomycin in an Experimental Methicillin-Resistant Staphylococcus aureus Bone and Joint Infection Model.

Staphylococcus aureus bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective, due to insufficient penetration into the infectious site. In an osteomyelitis model, the single local administration of nanoparticle-encapsulated daptomycin allows sterilization of the infectious sites after 4 and 14 days of treatment, while daily systemic daptomycin treatment for 4 days was not effective. These results demonstrate the great potential of this local antibiotic treatment.

Local characteristics associated with higher prevalence of ESBL-producing Escherichia coli in community-acquired urinary tract infections: an observational, cross-sectional study.

OBJECTIVES: The prevalence of ESBL-producing Escherichia coli (ESBL-E. coli) in community-acquired urinary tract infections (UTI) has been increasing worldwide since 2000, but with large geographical variations. The aim of this study was to determine whether the ESBL-E. coli rate in urine samples from individuals with community-acquired UTI was associated with the local socio-economic, environmental, agricultural and healthcare characteristics. METHODS: This was a cross-sectional study in western France using data on antibiotic susceptibility of E. coli isolated from urine samples of individuals with community-acquired UTI analysed in non-hospital laboratories from 2015 to 2017. The ESBL-E. coli rate was calculated for each laboratory. Data on socio-economic characteristics, human antibiotic consumption, hospital bed density, animal farming density and percentage of agricultural land and surface water were retrieved at the municipality level and aggregated by study area. Their association with ESBL-E. coli prevalence was quantified using multivariate linear regression models with a backward selection. RESULTS: From 358 291 E. coli isolates from urine samples tested in 92 laboratories, the mean ESBL-E. coli prevalence for the study period was 3.30%. In an adjusted model, the ESBL-E. coli rate was significantly (P < 0.05) and positively associated with the local percentage of people >65 years old, third-generation cephalosporin use (DDD/1000 inhabitants), number of hospital beds/km2, poultry density, pig density and percentage of agricultural land. Lower deprivation was associated with a higher ESBL-E. coli rate. CONCLUSIONS: Several anthropogenic factors (primary care, hospitals and animal farming) are associated with the local ESBL-E. coli rate in community-acquired UTI. These results could contribute to improve risk management, including identification of at-risk patient groups.

Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Play a Major Role in CD4+ T-Cell Impairment During Sepsis.

Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.

Pseudomonas aeruginosa Infection Impairs NKG2D-Dependent NK Cell Cytotoxicity through Regulatory T-Cell Activation.

Natural killer (NK) cells play a key role in both antibacterial and antitumor immunity. Pseudomonas aeruginosa infection has already been reported to alter NK cell functions. We studied in vitro the effect of P. aeruginosa on NK cell cytotoxic response (CD107a membrane expression) to a lymphoma cell line. Through positive and negative cell sorting and adoptive transfer, we determined the influence of monocytes, lymphocytes, and regulatory T cells (Treg) on NK cell function during P. aeruginosa infection. We also studied the role of the activating receptor natural killer group 2D (NKG2D) in NK cell response to B221. We determined that P. aeruginosa significantly altered both cytotoxic response to B221 and NKG2D expression on NK cells in a Treg-dependent manner and that the NKG2D receptor was involved in NK cell cytotoxic response to B221. Our results also suggested that during P. aeruginosa infection, monocytes participated in Treg-mediated NK cell alteration. In conclusion, P. aeruginosa infection impairs NK cell cytotoxicity and alters antitumor immunity. These results highlight the strong interaction between bacterial infection and immunity against cancer.

Trends in antimicrobial resistance among Escherichia coli from defined infections in humans and animals.

OBJECTIVES: To characterize and compare resistance trends in clinical Escherichia coli isolates from humans, food-producing animals (poultry, cattle and swine) and pets (dogs and cats). METHODS: Antibiogram results collected between January 2014 and December 2017 by MedQual [the French surveillance network for antimicrobial resistance (AMR) in bacteria isolated from the community] and RESAPATH (the French surveillance network for AMR in bacteria from diseased animals) were analysed, focusing on resistance to antibiotics of common interest to human and veterinary medicine. Resistance dynamics were investigated using generalized additive models. RESULTS: In total, 743 637 antibiograms from humans, 48 170 from food-producing animals and 7750 from pets were analysed. For each antibiotic investigated, the resistance proportions of isolates collected from humans were of the same order of magnitude as those from food-producing animals or pets. However, resistance trends in humans differed from those observed in pets and food-producing animals over the period studied. For example, resistance to third-generation cephalosporins and fluoroquinolones was almost always below 10% for both humans and animals. However, in contrast to the notable decreases in resistance observed in both food-producing animals and pets, resistance in humans decreased only slightly. CONCLUSIONS: Despite several potential biases in the data, the resistance trends remain meaningful. The strength of the parallel is based on similar data collection in humans and animals and on a similar statistical methodology. Resistance dynamics seemed specific to each species, reflecting different antibiotic-use practices. These results advocate applying the efforts already being made to reduce antibiotic use to all sectors and all species, both in human and veterinary medicine.

A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics.

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL-17A compared to control mice that resulted in an IL-17/IFN-γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL-10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL-10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL-10/IFN-γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.

Epidemiology of Community-Onset Severe Bacterial Infections in Children and Its Evolution: A Population-Based Study in France.

OBJECTIVES: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. DESIGN: Prospective, observational, population-based study from 2009 to 2014. SETTING: An administrative area accounting for 13% of the French pediatric population. PATIENTS: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. CONCLUSIONS: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent ß-Lactam-ß-Lactamase Inhibitor Combination.

Impeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum ß-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone ß-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of ß-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the in vivo efficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepime in vivo The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused by Enterobacteriaceae expressing ESBLs.

Live intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure: observations in an in vivo mouse model of prosthetic vascular material infections.

Objectives: To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs). Methods: We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI. Results: In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells. Conclusions: This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.

Vaccine-preventable severe morbidity and mortality caused by meningococcus and pneumococcus: A population-based study in France.

BACKGROUND: In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines. METHODS: We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated. RESULTS: Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs. CONCLUSIONS: Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy.

Adaptive processes of Staphylococcus aureus isolates during the progression from acute to chronic bone and joint infections in patients.

Staphylococcus aureus bone and joint infection (BJI) is associated with significant rates of chronicity and relapse. In this study, we investigated how S. aureus is able to adapt to the human environment by comparing isolates from single patients with persisting or relapsing BJIs that were recovered during the initial and recurrent BJI episodes. In vitro and in vivo assays and whole-genome sequencing analyses revealed that the recurrent isolates induced a reduced inflammatory response, formed more biofilms, persisted longer in the intracellular compartments of host bone cells, were less cytotoxic and induced less mortality in a mouse infection model compared with the initial isolates despite the lack of significant changes at the genomic level. These findings suggest that S. aureus BJI chronicization is associated with an in vivo bacterial phenotypical adaptation that leads to decreased virulence and host immune escape, which is linked to increased intraosteoblastic persistence and biofilm formation.

New Insight into Daptomycin Bioavailability and Localization in Staphylococcus aureus Biofilms by Dynamic Fluorescence Imaging.

Staphylococcus aureus is one of the most frequent pathogens responsible for biofilm-associated infections (BAI), and the choice of antibiotics to treat these infections remains a challenge for the medical community. In particular, daptomycin has been reported to fail against implant-associated S. aureus infections in clinical practice, while its association with rifampin remains a good candidate for BAI treatment. To improve our understanding of such resistance/tolerance toward daptomycin, we took advantage of the dynamic fluorescence imaging tools (time-lapse imaging and fluorescence recovery after photobleaching [FRAP]) to locally and accurately assess the antibiotic diffusion reaction in methicillin-susceptible and methicillin-resistant S. aureus biofilms. To provide a realistic representation of daptomycin action, we optimized an in vitro model built on the basis of our recently published in vivo mouse model of prosthetic vascular graft infections. We demonstrated that at therapeutic concentrations, daptomycin was inefficient in eradicating biofilms, while the matrix was not a shield to antibiotic diffusion and to its interaction with its bacterial target. In the presence of rifampin, daptomycin was still present in the vicinity of the bacterial cells, allowing prevention of the emergence of rifampin-resistant mutants. Conclusions derived from this study strongly suggest that S. aureus biofilm resistance/tolerance toward daptomycin may be more likely to be related to a physiological change involving structural modifications of the membrane, which is a strain-dependent process.

Propionibacterium namnetense sp. nov., isolated from a human bone infection.

A polyphasic taxonomic study was performed on two Gram-positive-staining, anaerobic, pleomorphic, rod-shaped strains isolated from human bone and tissue samples. Sequencing of the 16S rRNA genes revealed that the strains belong to a novel species within the genus Propionibacterium, most closely related to Propionibacterium acnes subsp. acnes and Propionibacterium acnes subsp. elongatum with similarity values of 98.4 % and 98.1 %, respectively. In addition, protein-coding genes for rpoB, recA and gyrB clearly separated the novel organism from all species and subspecies of the genus Propionibacterium. However, a DNA-DNA hybridization analysis between the novel organism and the type strain P. acnes ATCC 6919T revealed a value of only 61.1 %. Furthermore, whole genome analysis using the program OrthoANI gave a value of 88.5 %, which is significantly below the cut-off value of 95 % for species delineation. The major fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0. The DNA G+C content of the type strain was 59.7 mol%. When taken collectively, phenotypic, molecular genetic, chemotaxonomic and phylogenetic information demonstrate that the organism represents a distinct, albeit close relative of P. acnes On the basis of the results presented, the organism represents a novel member of the genus Propionibacterium for which the name Propionibacterium namnetense sp. nov. is proposed. The type strain is NTS 31307302T (=DSM 29427T=CCUG 66358T).

What is new in neonatal infection?

Diagnostic of early neonatal infection remains a serious challenge. Since clinical symptoms and biological markers are neither sensitive nor specific, a lot of newborns suspected of infection, undergo biological analysis and empirical antibiotic treatment awaiting bacteriological results. However the prevalence of the disease has dramatically decreased since the last twenty years, subsequently to the generalization of the per partum antibioprophylaxis strategy. Because the possible deleterious effects of neonatal antibiotic treatment are well described now, it appears very urgent to restrict their use to the infected newborns only. Recent studies underline the benefit of using procalcitonin (PCT) to diferentiate virai infections of bacterial infections. PCT in blood cord could become a new and efficient marker to help neonatologists taking care of infection-suspected newborns. An evidence based approach is necessary, combining anamnestic, clinical and biological data as PCT to identify the very low risk newborns population and to limit the neonatal antibiotic prescriptions.

Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study.

INTRODUCTION: Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. METHODS: Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. RESULTS: One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. CONCLUSIONS: We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.