Evolution of fluoroquinolone-resistant Escherichia coli in the gut after ciprofloxacin treatment.

BACKGROUND: Three healthy volunteers carried similar quinolone-resistant E. coli (QREC) (pulsed field gel electrophoresis profiles) in their gut before and after 14 days ciprofloxacin treatment. Given the intensity of the selective pressure and the mutagenic properties of quinolones, we determined whether these strains had evolved at the phenotypic and/or genomic levels. MATERIAL AND METHODS: Commensal QREC from before day-0 (D0), and a month after 14 days of ciprofloxacin (D42) were compared in 3 volunteers. Growth experiments were performed; acetate levels, mutation frequencies, quinolone MICs and antibiotic tolerance were measured at D0 and D42. Genomes were sequenced and single nucleotide polymorphisms (SNPs) between D0 and D42 were analyzed using DiscoSNP and breseq methods. Cytoplasmic proteins were extracted, HPLC performed and proteins identified using X!tandem software; abundances were measured by mass spectrometry using the Spectral Counting (SC) and eXtraction Ion Chromatograms (XIC) integration methods. RESULTS: No difference was found in MICs, growth characteristics, acetate concentrations, mutation frequencies, tolerance profiles, phylogroups, O-and H-types, fimH alleles and sequence types between D0 and D42. No SNP variation was evidenced between D0 and D42 isolates for 2/3 subjects; 2 SNP variations were evidenced in one. At the protein level, very few significant protein abundance differences were identified between D0 and D42. CONCLUSION: No fitness, tolerance, metabolic or genomic evolution of commensal QREC was observed overtime, despite massive exposure to ciprofloxacin in the gut. The three strains behaved as if they had been unaffected by ciprofloxacin, suggesting that gut may act as a sanctuary where bacteria would be protected from the effect of antibiotics and survive without any detrimental effect of stress.

Dimercaptosuccinic acid in combination with carbapenems against isogenic strains of Escherichia coli producing or not producing a metallo-ß-lactamase in vitro and in murine peritonitis.

BACKGROUND: Carbapenemase-producing Enterobacterales represent a major therapeutic challenge. MBLs, requiring zinc at their catalytic site, could be inhibited by meso-dimercaptosuccinic acid (DMSA), a heavy metal chelator already widely used for treating lead intoxication. OBJECTIVES: To evaluate the activity of carbapenems alone or combined with DMSA against MBL-producing Escherichia coli in a severe murine peritonitis model. METHODS: Isogenic strains of wild-type E. coli CFT073 producing the MBLs NDM-1, VIM-2 and IMP-1, and the control serine carbapenemases OXA-48 and KPC-3 were constructed. MIC determinations and time-kill assays were performed for imipenem, meropenem and ertapenem alone or in combination with DMSA. Infected mice were treated intraperitoneally for 24 h with imipenem, DMSA or their combination. Bacterial counts in peritoneal fluid and spleen were assessed at 24 h. RESULTS: DMSA in combination with each carbapenem caused a significant decrease in the MICs for all MBL-producing strains, in a concentration-dependent manner, but did not provide benefit against non-MBL strains. In mice infected with the NDM-1-producing strain, the combination of imipenem and DMSA significantly reduced bacterial counts in peritoneal fluid (P = 0.0006) and spleen (P < 0.0001), as compared with imipenem alone, with no benefit against the KPC-3-producing and CFT073 strains. DMSA concentrations in plasma of mice were comparable to those obtained in humans with a standard oral dose. CONCLUSIONS: DMSA restores the activity of carbapenems against MBL-producing strains, and its combination with carbapenems appears to be a promising strategy for the treatment of NDM-producing E. coli infections.

Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it.

BACKGROUND: Escherichia coli bloodstream infections (BSIs) account for high mortality rates (5%-30%). Determinants of death are unclear, especially since the emergence of ESBL producers. OBJECTIVES: To determine the relative weight of host characteristics, bacterial virulence and antibiotic resistance in the outcome of patients suffering from E. coli BSI. METHODS: All consecutive patients suffering from E. coli BSI in seven teaching hospitals around Paris were prospectively included for 10 months. E. coli isolates were sequenced using Illumina NextSeq technology to determine the phylogroup, ST/ST complex (STc), virulence and antimicrobial resistance gene content. Risk factors associated with death at discharge or Day 28 were determined. RESULTS: Overall, 545 patients (mean ± SD age 68.5 ±âŸ16.5 years; 52.5% male) were included. Mean Charlson comorbidity index (CCI) was 5.6 (± 3.1); 19.6% and 12.8% presented with sepsis and septic shock, respectively. Portals of entry were mainly urinary (51.9%), digestive (41.9%) and pulmonary (3.5%); 98/545 isolates (18%) were third-generation cephalosporin resistant (3GC-R), including 86 ESBL producers. In-hospital death (or at Day 28) was 52/545 (9.5%). Factors independently associated with death were a pulmonary portal of entry [adjusted OR (aOR) 6.54, 95% CI 2.23-19.2, P = 0.0006], the iha_17 virulence gene (aOR 4.41, 95% CI 1.23-15.74, P = 0.022), the STc88 (aOR 3.62, 95% CI 1.30-10.09, P = 0.014), healthcare-associated infections (aOR 1.98, 95% CI 1.04-3.76, P = 0.036) and high CCI (aOR 1.14, 95% CI 1.04-1.26, P = 0.006), but not ESBL/3GC-R. CONCLUSIONS: Host factors, portal of entry and bacterial characteristics remain major determinants associated with mortality in E. coli BSIs. Despite a high prevalence of ESBL producers, antibiotic resistance did not impact mortality. (ClinicalTrials.gov identifier: NCT02890901.).

Activity of fosfomycin alone or combined with temocillin in vitro and in a murine model of peritonitis due to KPC-3- or OXA-48-producing Escherichia coli.

Background: Alternative therapeutic regimens are urgently needed against carbapenemase-producing Enterobacteriaceae. Fosfomycin often remains active against KPC and OXA-48 producers, but emergence of resistance is a major limitation. Our aim was to determine whether the association of temocillin with fosfomycin might be useful to treat KPC- or OXA-48-producing Escherichia coli infections. Methods: Isogenic derivatives of E. coli CFT073 with blaKPC-3- or blaOXA-48-harbouring plasmids (named CFT073-KPC-3 and CFT073-OXA-48, respectively) were used. The addition of temocillin to fosfomycin was tested using the chequerboard method and time-kill curves as well as in a fatal peritonitis murine model. Mice were treated for 24 h with fosfomycin alone or in combination with temocillin. Bacterial loads, before and after treatment, were determined in the peritoneal fluid and fosfomycin-resistant mutants were detected. Results: Temocillin MICs were 8, 32 and 256 mg/L for CFT073 (WT), CFT073-KPC-3 and CFT073-OXA-48, respectively. Fosfomycin MIC was 0.5 mg/L for all strains. The chequerboard experiments demonstrated synergy for all three strains. In time-kill curves, combining temocillin with fosfomycin was synergistic, bactericidal and prevented emergence of resistance for CFT073-pTOPO and CFT073-KPC-3, but not CFT073-OXA-48. In vivo, for the three strains, bacterial counts were lower in peritoneal fluid with the combination compared with fosfomycin alone (P < 0.001) and inhibited growth of resistant mutants in all cases. Conclusions: The combination of fosfomycin and temocillin demonstrated a benefit in vitro and in vivo against E. coli strains producing KPC-3 or OXA-48-type carbapenemases. This combination prevented the emergence of fosfomycin resistance and proved to be more bactericidal than fosfomycin alone.

Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses.

Pneumonia due to either Streptococcus pneumoniae (Sp) or Staphylococcus aureus (Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P = 0·03 and P = 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2% vs. 27·9%, P = 0·03) but not Sa carriage (11·6% vs. 14%, P = 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4-3·1; with a relative excess risk due to interaction of -0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1-4·3, P = 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.

Quinolone-resistant Escherichia coli from the faecal microbiota of healthy volunteers after ciprofloxacin exposure are highly adapted to a commensal lifestyle.

OBJECTIVES: Quinolone-resistant Escherichia coli (QREC) primarily emerge in commensal bacteria under selective pressure. The aim of this work was to investigate the characteristics of QREC from the faecal microbiota after quinolone exposure, as they remain largely unknown. METHODS: Forty-eight healthy volunteers received ciprofloxacin from day 1 to day 14. QREC were detected in stools from 14 subjects at day 42. QREC were compared in terms of genetic background, metabolic properties, stress resistance and intestinal colonization abilities with quinolone-susceptible E. coli (QSEC) from the same 14 individuals and from 29 volunteers who remained QREC-free. RESULTS: QREC always belonged to a single clone for a given volunteer and to restricted phylogenetic groups. QREC carried significantly more iron capture systems than QSEC. Maximum growth rates in minimal medium with gluconate, general stress regulator RpoS activity assessed by iodine staining and resistance to oxidative and acid stresses were significantly higher for QREC than for QSEC. In a mouse colonization model, QREC efficiently colonized the intestine microbiota despite the presence of QSEC competitors. At day 42, QREC and QSEC faecal counts from the 14 volunteers were comparable except in three subjects where only QREC could be detected. CONCLUSIONS: These results suggest that QREC do not have a fitness cost, probably as a result of genetic co-selection, but are highly adapted to a commensal lifestyle. They may not be eliminated easily from the faecal microbiota from healthy subjects once selected.

Lymphoma and Epstein-Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial.

OBJECTIVES: Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein-Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients. We assessed whether IL-2 had an impact on EBV replication and the development of lymphoma. METHODS: A total of 130 ART-naïve patients were randomized to receive IL-2 therapy (n = 66) or no treatment (n = 64). Clinical data for patients with lymphomas were reviewed and tumours assessed for evidence of EBV infection and CD25 (the IL-2 receptor) expression. EBV DNA levels were measured in whole blood and plasma in both arms using real-time polymerase chain reaction (PCR), up to 48 weeks after baseline (BL). RESULTS: Four lymphomas occurred, a median of 61 weeks [range 40-94 weeks] after randomization at a median CD4 cell count of 396 cells/µL (IQR 234-536 cells/µL). In the IL-2 arm, two patients developed EBV-positive Hodgkin's lymphoma, and one developed EBV-negative Burkitt-type lymphoma. One patient in the control group developed EBV-positive non-Hodgkin's lymphoma. CD25 was negative in all cases. Among the 41 of 55 (control arm) and 44 of 58 (IL-2 arm) patients with detectable EBV DNA in whole blood at both BL and week 48, the median change in EBV DNA between BL and week 48 was +0.04 log10 copies/ml in both arms (P = 0.7). In plasma, EBV was detected at least once in 22 of 52 controls and 21 of 54 IL-2-treated patients (P = 0.8). CONCLUSIONS: IL-2 therapy had no significant effect on EBV replication over 48 weeks in these ART-naïve patients. The occurrence of lymphomas did not seem to be associated with IL-2 therapy.

Invasive pneumococcal disease in HIV-infected adults in France from 2000 to 2011: antimicrobial susceptibility and implication of serotypes for vaccination.

PURPOSE: Invasive pneumococcal diseases (IPD) remain frequent and severe events in human immunodeficiency virus (HIV)-infected subjects despite the use of antiretroviral therapy and the availability of vaccines. Our aim was to assess the antibiotic susceptibilities and serotypes of strains responsible for IPD in HIV-infected patients. METHODS: We retrospectively analyzed all Streptococcus pneumoniae strains isolated from normally sterile sites between 2000 and 2011 in HIV-infected patients from a single reference center in Paris. The minimum inhibitory concentrations were determined by the E-test, and serotyping was performed by the antiserum agglutination method. RESULTS: Among our study group, 41 HIV-infected adults presented 43 IPD during the study period. Of these 41 patients, 78 % were men, and the median age was 43 (range 23-62) years. the median CD4 cell count was 184/mm(3) (6-1,090/mm(3)), 51 % were receiving antiretroviral therapy, and 24 % had plasma HIV-RNA levels of <400 copies/mL. Only two patients had received the pneumococcal polysaccharide 23-valent vaccine (PPV23). Isolates were susceptible to penicillin G, amoxicillin, and cotrimoxazole in 44, 70, and 59 % of cases, respectively, and were significantly less susceptible to these antibiotics than isolates in the French general population during the same period. Among the 27 strains serotyped, 18 different serotypes were observed, of which 19A, 14, 7F, and 6A were the most frequent. Serotype distribution was similar to that in the French general population. The PPV23 vaccine and the 13-valent conjugate vaccine (PCV13) would have theoretically covered 78 and 70 % of cases, respectively. CONCLUSIONS: In our HIV-infected patient cohort, S. pneumoniae isolates demonstrated higher levels of resistance to beta-lactamines and cotrimoxazole than in the French general population. HIV-infected patients should benefit from the herd protection effect expected from the large-scale vaccination of children by PCV13.

Clinical predictive values of extended-spectrum beta-lactamase carriage in patients admitted to medical wards.

We aimed to reassess, through clinical items, populations at risk for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage at admission to hospital and to assess the risk of further positive clinical culture of ESBL-E among carriers. We performed a 5-month cohort study in a medicine ward of a 500-bed university teaching hospital in the Parisian area of France. All admitted patients were prospectively enrolled for rectal swabbing and clinical data collection, including bacterial infection at admission and during stay. Variables associated with ESBL-E carriage were identified by univariate and multivariate analysis. Five hundred patients were included. The prevalence of ESBL-E was 6.6% (33/500) upon admission. Only previous carriage of multidrug-resistant bacteria (MDRB) was associated with carriage (odds ratio [OR]: 17.7, 95% confidence interval (CI) 5.8-54.2, p < 0.001), yet, the positive predictive value (PPV) was not higher than 50%. When prior MDRB carriage was not considered in the multivariate analysis, only prior antibiotic consumption was found to be associated with carriage at admission (OR: 2.2 [1.1-4.5], p = 0.02). Two patients had ESBL-E infection at admission, yet, no patient became infected with ESBL-E during their stay. The clinical prediction of ESBL carriage at admission in our wards was found to be poorly efficient for assessing the at-risk population.

The intravenous vancomycin prescription practices of French infectious disease specialists: A cross-sectional observational study.

INTRODUCTION: Vancomycin prescription modalities remain non-consensual. We examined and evaluated the vancomycin prescription habits of infectious disease specialists in France. METHODS: Through an anonymized online questionnaire sent to members of the French Infectious Diseases Society, detailed information on vancomycin prescription modalities was collected. RESULTS: Out of the 712 physicians contacted, 179 (25%) completed the questionnaire; 174 (97%) of them routinely prescribed intravenous vancomycin: 95 (55%) by continuous infusion only, 12 (7%) by intermittent infusion, while 67 (38%) used the two modalities. Among continuous administration users, 157 (97%) applied a loading dose of 15 mg/kg or less (n = 80, 49%), 20-25 mg/kg (n = 33, 20%), or 30 mg/kg or more (n = 45, 28%); 143 (88%) used a maintenance dosage of 30 mg/kg/day and 157 (97%) carried out drug monitoring. CONCLUSION: In France, infectious disease specialists favor continuous administration of vancomycin using a loading dose, with systematic monitoring of vancomycin serum concentrations.

[Attitude and beliefs of healthcare workers toward influenza vaccination in Internal Medicine: A cross-sectional survey]. / Attitude et croyances du personnel soignant en Médecine Interne vis-à-vis de la vaccination antigrippale saisonnière : étude transversale descriptive.

INTRODUCTION: The rate of vaccination in HCWs in France remains low. We aimed to analyze the attitude and beliefs of HCWs toward influenza vaccination in Internal Medicine wards. METHODS: We conducted a cross-sectional survey of HCWs in the departments of Internal Medicine of two tertiary hospitals in France. An anonymous questionnaire designed for this study was used to collect demographic, health beliefs and attitudes, and medical knowledge related to the influenza and influenza vaccine. The survey started shortly prior the 2019 influenza season. RESULTS: The surveys were completed by 158 (29[18-62] years-old ; 75.9% female ; 69.6% non-medical workers) of 187 (84.5%) HCWs. Overall, influenza vaccination coverage rate was 50.6% (n=80/158). Higher vaccination coverage was found in physician and in HCWs who had a better knowledge about the virus transmission. The reason to fulfill vaccination recommendations was to protect the patients, their relatives and themselves for more than 80% of HCWs compliant to vaccination recommendation. More than a third of HCWs (n=59/158; 37.3%) refused to be vaccinated or hesitated. Among them, 12 (12/59, 20.3%) believed that influenza vaccine could cause flu. The main reasons for reluctant HCWs to eventually accept to be vaccinated were a mandatory vaccination program and the demonstration of a better vaccine efficacy to prevent the disease. CONCLUSION: Influenza vaccination coverage among HCWs in Internal Medicine remains low. Education campaigns targeting in priority nurses and nurse assistants is mandatory to improve the compliance of HCWs to vaccination recommendation.

Acute cholangitis: Diagnosis and management.

Acute cholangitis is an infection of the bile and biliary tract which in most cases is the consequence of biliary tract obstruction. The two main causes are choledocholithiasis and neoplasia. Clinical diagnosis relies on Charcot's triad (pain, fever, jaundice) but the insufficient sensitivity of the latter led to the introduction in 2007 of a new score validated by the Tokyo Guidelines, which includes biological and radiological data. In case of clinical suspicion, abdominal ultrasound quickly explores the biliary tract, but its diagnostic capacities are poor, especially in case of non-gallstone obstruction, as opposed to magnetic resonance cholangiopancreatography and endoscopic ultrasound, of which the diagnostic capacities are excellent. CT scan is more widely available, with intermediate diagnostic capacities. Bacteriological sampling through blood cultures (positive in 40% of cases) and bile cultures is essential. A wide variety of bacteria are involved, but the main pathogens having been found are Escherichia coli and Klebsiella spp., justifying first-line antimicrobial therapy by a third-generation cephalosporin. Systematic coverage of Enterococcus spp. and anaerobic infections remains debated, and is usually recommended, in case of severity criteria for Enterococcus severity levels, or anaerobic bilio-digestive anastomosis for anaerobes. Presence of a biliary stent is the only identified risk-factor associated with infections by multidrug-resistant pathogens. Along with antimicrobial therapy, endoscopic or radiological biliary drainage is a crucial management component. Despite improved management, mortality in cases of acute cholangitis remains approximately 5%.

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.

OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

[Should doses of antibiotics be adjusted?] / Faut-il proposer une adaptation posologique lors d'une antibiothérapie ?

While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve therapeutic success and to limit the risks of the emergence of resistance. The optimization of antibiotic use and dosages must have a threefold objective: guarantee antibacterial efficacy, limit toxicities and limit emergence of resistant strains. However, with the increase in the number of multipathological patients, particularly those with renal or hepatic impairment, the increase in the number of patients with extreme weights and the use of antibiotics with narrower therapeutic margins, the adaptation of antibiotic dosages is becoming increasingly important. By reminding some principles of pharmacokinetics and pharmacodynamics of antibiotics (PK/PD), the necessary objectives for clinical effectiveness of most antibiotic classes are reviewed and several examples of situations where dosage adjustments are necessary will be given. In particular, adjustment of antibiotic dosages in obese patients will be discussed. Adaptation is not limited to the adaptation of the total daily dose. The PK/PD parameters also tell us that the mode of administration (intermittent versus continuous, number of injections per day, etc.) is also an essential point to consider. By taking examples concerning some molecules, infections and difficult clinical situations, we review situations in which dosage adjustments appear necessary.

[Influenzae and pneumococcal vaccination rate in an internal medicine ward]. / Couverture vaccinale antigrippale et antipneumococcique dans un service de médecine interne.

INTRODUCTION: Vaccination against influenza virus and Streptococcus pneumoniae is a global health priority and authorities, on the basis of recent publications, have recently updated French recommendations. The aim of this study was to describe the influenzae and pneumococcal vaccination's rate in an internal medicine ward. MATERIAL AND METHODS: All patients consecutively hospitalized during a 10 week-period in an internal medicine ward were included. The reasons for non-vaccination and the impact of an educational program for corrective measures were reported. RESULTS: Overall, 198 consecutive patients were included; 93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of them were vaccinated against these microorganisms, respectively. Prior pneumococcal vaccination was more frequently observed in immunocompromised patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but no significant difference was observed for influenza vaccine. Corrective measures were initiated in 46 patients (39%), non-immunized against S. pneumoniae. CONCLUSION: These results underline the very low prevalence of pneumococcal vaccination rate in at-risk hospitalized patients, as compared with influenza, despite recent recommendations.

[Pyogenic brain abscesses in adults]. / Abcès cérébraux à pyogènes de l'adulte.

Pyogenic brain abscesses (BA) are rare and their diagnosis may be difficult because of the absence of specific clinical or biological signs. However, the use of diffusion-weighted brain MRI sequences has modified the management of BA, as they are highly sensitive and specific to differentiate pyogenic brain abscesses from necrotic tumors, which are the most frequent differential diagnosis in case of ring-enhancing lesions on CT scan. This new tool allows for a rapid diagnosis and should be followed by a CT-guided aspiration of BA. This safe procedure should be performed if possible before starting antibiotics in order to optimize microbiological diagnosis. Recent epidemiological changes include an increase in the numbers of immunocompromised patients and a decrease in the traditional causes of BA (direct inoculation, ear nose and throat infections, etc.). In consequence, a wider range of bacterial species may be involved, making it all the more necessary to obtain a microbiological diagnosis. Many uncertainties remain in terms of the duration of antibiotic treatment, the optimal radiological follow-up and the place for associated treatments such as corticosteroids and anticonvulsive therapy. BA remain severe infections with high mortality and morbidity rates; the factor most regularly associated with a poor prognosis is the patients neurological status at diagnosis.

[Resistance to fluoroquinolones in 2013: what are the consequences in internal medicine?]. / Résistance aux fluoroquinolones en 2013 : quel impact pour l'interniste ?

Because of their important qualities, fluoroquinolones are amongst the most prescribed antibiotics in the world. The corollary of this success is the rapid increase in resistance to fluoroquinolones, responsible for treatment failures. Moreover, fluoroquinolone-resistance is often accompanied by resistance to other classes of antibiotics. Currently, significant levels of resistance are found both in hospitals and in community settings, severely limiting possibilities for empirical use of fluoroquinolones. A major mechanism explaining the rapid emergence of resistance to fluoroquinolones is their specific impact on human microbiota and the selection of resistant strains in the microbiota, which seems to be an unavoidable ecological side effect. In order to preserve the efficiency of this important class of antibiotics, limiting their use and respecting good practice recommendations are essential.