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1.
Eur J Clin Microbiol Infect Dis ; 43(1): 95-104, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37964043

ABSTRACT

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


Subject(s)
Endocarditis, Bacterial , Endocarditis , Heart Valve Prosthesis , Aged , Humans , Aminoglycosides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Duration of Therapy , Endocarditis/drug therapy , Endocarditis/etiology , Endocarditis, Bacterial/microbiology , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis/microbiology , Prognosis , Reinfection , Retrospective Studies , Streptococcus
2.
Int J Antimicrob Agents ; 62(2): 106885, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37302771

ABSTRACT

OBJECTIVES: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. METHODS: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. RESULTS: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT>MIC = 100% and to 6% for AUC0-24h/MIC > 60, even with high clindamycin dose. CONCLUSION: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains.


Subject(s)
Rifampin , Staphylococcal Infections , Humans , Rifampin/therapeutic use , Clindamycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus , Microbial Sensitivity Tests
3.
Infect Dis Now ; 52(5): 273-279, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35636701

ABSTRACT

BACKGROUND: Optimized antibiotic plasma predictor efficacy is essential in systemic infections. The uricosuric agent probenecid inhibits tubular excretion of antibiotics and may be used as ß-lactam pharmacokinetic enhancer (BLPKE), even though few data are currently available for this purpose. METHODS: We conducted a monocentric and retrospective observational study including all patients who received probenecid in combination with parenteral ß-lactam antibiotics for systemic infections from Jan 1, 2014 to Dec 31, 2019. Demographics, infection characteristics, treatment and ATC (antibiotics trough concentration) were investigated. RESULTS: All in all, 38 patients were included. Eight patients had a history of sickle cell disease. Hyperfiltration (defined as eGFR>130mL/min/1.73m2) was detected in twenty-one patients including six with sickle cell disease. Probenecid (500mg q6h orally) was added to antibiotics for a median (IQR) of 13 days (6.75-21.75), after a median (IQR) time lapse of 7 days (4-16) following the initiation of antibiotics. Probenecid was administered for low antibiotic trough concentration in 29 patients, for increased renal clearance in 5 patients and for persisting fever despite antibiotic therapy in 4 patients (including 1 infective relapse). A second plasma trough concentration, following probenecid administration, was available in 19 patients within a median (IQR) 3 days (2-5). Probenecid induced increased ATC in 18/19 patients (94.7%), with a median (IQR) change of +228.4% (IQR 38.7-633). No major adverse effects were reported. CONCLUSION: Probenecid could be a BLPKE. Our data suggest this drug should be used more often to optimize ß-lactam pharmacokinetics in clinical practice.


Subject(s)
Anemia, Sickle Cell , Probenecid , Anti-Bacterial Agents/therapeutic use , Humans , Probenecid/pharmacokinetics , Probenecid/therapeutic use , Retrospective Studies , beta-Lactams/therapeutic use
4.
Emerg Microbes Infect ; 10(1): 929-938, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33913790

ABSTRACT

Context: Today, infective endocarditis (IE) caused by Enterococcus faecalis represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. Material and methods: To further study the in situ genetic microdiversity and its possible phenotypic manifestations in E. faecalis IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. Results: By sequencing a total of 58 E. faecalis genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors ebpA/B/C, and srtC, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the in-vitro phenotypic heterogeneity, growth, and early biofilm production. Conclusion: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses.


Subject(s)
Endocarditis, Bacterial/microbiology , Enterococcus faecalis/classification , Genetic Variation , Gram-Positive Bacterial Infections/microbiology , Aged , Aged, 80 and over , Codon, Nonsense , Enterococcus faecalis/genetics , Enterococcus faecalis/isolation & purification , Female , Genome, Bacterial , Heart Valves/microbiology , Humans , Male , Phenotype , Sequence Deletion , Whole Genome Sequencing
5.
Rev Med Interne ; 42(6): 411-420, 2021 Jun.
Article in French | MEDLINE | ID: mdl-33234320

ABSTRACT

Intravenous catheters are multiple and essential for daily practice. They are also responsible for high morbidity and mortality. Simple or echo-guided peripheral venous catheters, midlines, PICCline, tunneled or non-tunneled central venous catheters, and implantable venous access device are currently at our disposal. Thus, catheter selection, duration and indications for use, and prevention and treatment of complications vary according to the situation. The objective of this update is to provide the clinician with an overview of knowledge and rules of good practice on the use of catheters.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Catheters , Humans
6.
J Antimicrob Chemother ; 75(8): 2334-2343, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32417924

ABSTRACT

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.).


Subject(s)
Bacteremia , Escherichia coli Infections , Sepsis , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/epidemiology , Escherichia coli/genetics , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Paris , Risk Factors , Sepsis/drug therapy , beta-Lactamases/genetics
7.
Eur J Clin Microbiol Infect Dis ; 39(1): 121-129, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31512147

ABSTRACT

Cefoxitin has demonstrated good in vitro activity against extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) and is regarded as a carbapenem-sparing beta-lactam alternative in urinary tract infections. Its efficacy has never been compared to carbapenems in male UTIs. Our study aimed to compare the clinical and microbiological efficacy of cefoxitin (FOX) and carbapenems (CP) in febrile M-UTI due to ESBL-Ec (F-M-UTI). We conducted a multicenter retrospective cohort study of patients with F-M-UTI treated with FOX or CP as definitive therapy, between January 2013 and June 2015, in six French acute care teaching hospitals. The clinical and microbiological efficacies of FOX and CP were compared using multivariable logistic regression models, adjusting for propensity scores. Of the 66 patients included, 23 patients in FOX group and 27 in CP group had clinical assessment at follow-up. Median follow-up after end of treatment was 63 days (interquartile range 26-114). Clinical success was observed for 17/23 (73.9%) and 22/27 (81.5%) patients and microbiological success for 11/19 (57.9%) and for 6/12 (50.0%) patients in FOX and CP groups respectively. We did not find any significant difference for clinical (OR = 0.90, 95% CI [0.12; 6.70]) neither microbiological (OR = 0.85, 95% CI [0.05; 14.00]) success between CP and FOX groups in univariate and multivariable models. In the FOX group, high dose with use of continuous infusion was associated with clinical success. These results add evidence that FOX is an effective alternative treatment to carbapenems for M-UTI caused by ESBL-Ec, particularly when high doses and continuous infusion are used.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Cefoxitin/therapeutic use , Escherichia coli Infections/drug therapy , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , Aged , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli Infections/microbiology , Fever/microbiology , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , beta-Lactamases
8.
Med Mal Infect ; 50(1): 49-56, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31088757

ABSTRACT

BACKGROUND: Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. METHODS: We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. RESULTS: A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P=0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. CONCLUSION: Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.


Subject(s)
Acute Chest Syndrome/microbiology , Anemia, Sickle Cell/microbiology , Fever/microbiology , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/diagnosis , Acute Chest Syndrome/complications , Adult , Anemia, Sickle Cell/complications , Bacteria/genetics , Bacteria/isolation & purification , Female , Fever/etiology , Humans , Male , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Pneumonia, Bacterial/microbiology , Pneumonia, Viral/virology , Viruses/genetics , Viruses/isolation & purification , Young Adult
11.
Rev Med Interne ; 39(6): 386-392, 2018 Jun.
Article in French | MEDLINE | ID: mdl-29571580

ABSTRACT

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.


Subject(s)
Influenza, Human/prevention & control , Internal Medicine , Patient Admission/statistics & numerical data , Pneumonia, Pneumococcal/prevention & control , Vaccination/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , France/epidemiology , Hospital Units/statistics & numerical data , Humans , Immunocompromised Host , Influenza Vaccines/therapeutic use , Influenza, Human/epidemiology , Internal Medicine/statistics & numerical data , Male , Middle Aged , Pneumococcal Vaccines/therapeutic use , Pneumonia, Pneumococcal/epidemiology , Prevalence , Streptococcus pneumoniae/immunology , Young Adult
12.
J Hosp Infect ; 99(4): 481-486, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29477634

ABSTRACT

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers. METHODS: A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT. RESULTS: Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3-79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0-77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported. CONCLUSION: CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carrier State/therapy , Enterobacteriaceae Infections/therapy , Fecal Microbiota Transplantation , Gram-Positive Bacterial Infections/therapy , Vancomycin-Resistant Enterococci/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Bacteriological Techniques , Carrier State/microbiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Enterobacteriaceae Infections/microbiology , Feces/microbiology , Female , Gram-Positive Bacterial Infections/microbiology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Treatment Outcome , Young Adult
13.
Br J Dermatol ; 177(6): 1575-1582, 2017 12.
Article in English | MEDLINE | ID: mdl-28452064

ABSTRACT

BACKGROUND: Necrotizing soft-tissue infections (NSTI) are rare, life-threatening conditions. OBJECTIVES: To assess whether admitting hospital characteristics were associated with NSTI mortality. METHODS: We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in the period 2007-12 with an International Classification of Diseases 10 code of necrotizing fasciitis were eligible. We extracted data on the patients (age, sex, intensive care unit admission, comorbidities) and hospitals (public vs. private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥ 3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of 28-day mortality and in-hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively. RESULTS: We identified 1537 patients (915 males) with a median age of 60 years (interquartile range 48-75), admitted to 326 hospitals, public (82%) and admitting < 3 NSTI cases/year (93%). Overall, 364 patients died [23·7%; 95% confidence interval (CI) 21·6-25·9]. Patients treated in public teaching centres with ≥ 3 NSTI cases annually had lower 28-day mortality (adjusted odds ratio 0·68; 95% CI 0·46-0·99; P = 0·045) and in-hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and interhospital transfer. CONCLUSIONS: Our findings highlight an increased survival in teaching centres with high-volume NSTI procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.


Subject(s)
Fasciitis, Necrotizing/mortality , Aged , Female , France/epidemiology , Hospital Mortality , Hospitalization/statistics & numerical data , Hospitals, Private/statistics & numerical data , Hospitals, Public/statistics & numerical data , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Patient Transfer/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors
14.
J Hosp Infect ; 95(4): 433-437, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28237504

ABSTRACT

Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe.


Subject(s)
Carrier State/microbiology , Carrier State/therapy , Drug Resistance, Bacterial , Enterobacteriaceae/isolation & purification , Fecal Microbiota Transplantation/methods , Vancomycin-Resistant Enterococci/isolation & purification , Adult , Aged , Aged, 80 and over , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/therapy , Female , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/therapy , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Treatment Outcome
15.
Antimicrob Agents Chemother ; 60(1): 424-30, 2016 01.
Article in English | MEDLINE | ID: mdl-26525800

ABSTRACT

We investigated the efficacies of cefotaxime (CTX) and amoxicillin (AMX)-clavulanate (CLA) (AMC) against extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli in vitro and in a murine model of urinary tract infection (UTI). MICs, the checkerboard dilution method, and time-kill curves were used to explore the in vitro synergism between cefotaxime and amoxicillin-clavulanate against two isogenic E. coli strains-CFT073-RR and its transconjugant, CFT073-RR Tc bla(CTX-M-15)-harboring a bla(CTX-M-15) plasmid and a bla(OXA-1) plasmid. For in vivo experiments, mice were separately infected with each strain and treated with cefotaxime, amoxicillin, and clavulanate, alone or in combination, or imipenem, using therapeutic regimens reproducing time of free-drug concentrations above the MIC (fT≥MIC) values close to that obtained in humans. MICs of amoxicillin, cefotaxime, and imipenem were 4/>1,024, 0.125/1,024, and 0.5/0.5 mg/liter, for CFT073-RR and CFT073-RR Tc bla(CTX-M-15), respectively. The addition of 2 mg/liter of clavulanate (CLA) restored the susceptibility of CFT073-RR Tc bla(CTX-M-15) to CTX (MICs of the CTX-CLA combination, 0.125 mg/liter). The checkerboard dilution method and time-kill curves confirmed an in vitro synergy between amoxicillin-clavulanate and cefotaxime against CFT073-RR Tc bla(CTX-M-15). In vivo, this antibiotic combination was similarly active against both strains and as effective as imipenem. In conclusion, the cefotaxime and amoxicillin-clavulanate combination appear to be an effective, easy, and already available alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains.


Subject(s)
Amoxicillin-Potassium Clavulanate Combination/pharmacology , Anti-Bacterial Agents/pharmacology , Cefotaxime/pharmacology , Pyelonephritis/drug therapy , Urinary Tract Infections/drug therapy , Uropathogenic Escherichia coli/drug effects , beta-Lactamases/genetics , Amoxicillin-Potassium Clavulanate Combination/blood , Amoxicillin-Potassium Clavulanate Combination/pharmacokinetics , Animals , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacokinetics , Cefotaxime/blood , Cefotaxime/pharmacokinetics , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Female , Gene Expression , Humans , Imipenem/pharmacology , Mice , Mice, Inbred CBA , Microbial Sensitivity Tests , Plasmids/chemistry , Plasmids/metabolism , Pyelonephritis/blood , Pyelonephritis/microbiology , Pyelonephritis/pathology , Urinary Tract Infections/blood , Urinary Tract Infections/microbiology , Urinary Tract Infections/pathology , Uropathogenic Escherichia coli/enzymology , Uropathogenic Escherichia coli/genetics , beta-Lactam Resistance/genetics , beta-Lactamases/metabolism
16.
J Antimicrob Chemother ; 70(5): 1466-72, 2015 May.
Article in English | MEDLINE | ID: mdl-25564564

ABSTRACT

OBJECTIVES: Temocillin is a 6α-methoxy derivative of ticarcillin that is resilient to ESBLs. Prospective data about its in vivo activity remain scarce. Our aims were: (i) to evaluate the activity of temocillin in a urinary tract infection (UTI) model due to ESBL-producing Escherichia coli and compare it with that of imipenem; and (ii) to define in vivo susceptibility breakpoints. METHODS: Mice were infected with a susceptible E. coli CFT073-RR or its transconjugant (CFT073-RR Tc) harbouring a blaCTX-M-15-carrying plasmid, using an ascending UTI model. Therapeutic regimens were chosen in order to reproduce percentage of time of free drug concentrations above MIC (fT>MIC) obtained in humans with standard regimens of temocillin (200 mg/kg every 2 h for 2 g every 12 h) or imipenem (100 mg/kg every 2 h for 1 g every 8 h). Additional regimens of temocillin (200 mg/kg every 4 and 6 h) with reduced fT>MIC were studied. RESULTS: MICs of temocillin and imipenem were 4/8 and 0.5/0.5 mg/L, for CFT073-RR and CFT073-RR Tc, respectively. In vivo, when given every 2 h (fT>MIC = 82% and 70%), temocillin was bactericidal and as effective as imipenem in kidneys against both strains without selecting resistant mutants. Temocillin remained active even when given every 4 h, generating an fT>MIC of 41% and 35%, which corresponded to a breakpoint of 16 mg/L in humans with the standard regimen. CONCLUSIONS: Our observations support the consideration of a standard regimen of temocillin as an alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains with an MIC of 16 mg/L or less.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Escherichia coli Infections/drug therapy , Escherichia coli/enzymology , Penicillins/administration & dosage , Urinary Tract Infections/drug therapy , beta-Lactamases/metabolism , Animals , Disease Models, Animal , Escherichia coli Infections/microbiology , Female , Imipenem/administration & dosage , Mice, Inbred CBA , Microbial Sensitivity Tests , Treatment Outcome
17.
Rev Med Interne ; 36(5): 339-45, 2015 May.
Article in French | MEDLINE | ID: mdl-25579464

ABSTRACT

Measles is a highly contagious infectious disease, which needs more than 95% worldwide vaccination coverage of 2 doses to be eradicated. Despite an important involvement of the WHO for massive immunization, goals have not bean reached, and outbreaks can occur at any time in many countries, including Western Europe. In France, 22,000 cases were identified between 2009 and 2011, mainly in infants and young adults, which are not or not enough vaccinated (one dose). In 2012, even though the number of cases has drastically decreased, the outbreak is still going on, especially in South of France. That is why every clinician needs to be concerned about the clinical manifestations of the disease, and its complications. Besides a febrile rash, measles is often responsible of pneumonia and biologic hepatitis in adults. Hepatitis does not seem frequent in children. Clinicians need to be aware of specific complications, like encephalitis in case of cellular immunodepression, high risk of pneumonia in pregnant women. In patients previously vaccinated, incidence of complications is the same but patients are not contagious. Even if measles diagnosis is clinical, blood confirmation by serology is recommended in France when possible. Outcome is mainly favourable, but measles is not well-tolerated with high levels of hospitalisation even without any complication. Vaccination is the only way to protect against it.


Subject(s)
Measles , Adult , Child , Child, Preschool , Disease Outbreaks , Female , France/epidemiology , Humans , Incidence , Infant , Mass Vaccination , Measles/complications , Measles/epidemiology , Measles/prevention & control , Measles/virology , Measles Vaccine/therapeutic use , Pregnancy , Young Adult
18.
Ann Fr Anesth Reanim ; 33(12): 638-42, 2014 Dec.
Article in French | MEDLINE | ID: mdl-25458455

ABSTRACT

OBJECTIVES: Necrotizing fasciitis (NF) are rare and severe soft tissue infections associated with a high mortality rate. In order to assess the management of NF in French-speaking intensive care units (ICUs), we conducted a survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR). STUDY DESIGN: Online self-administered survey. METHODS: A link to an online survey was sent by email to 4620 anesthesiologists and/or intensivists and was available online from January to February 2014. RESULTS: One hundred and seventy-five physicians (3.8%) who worked in 135 ICUs filled out the online survey. Among respondents, 42% reported having managed up to two patients with NF during the previous year; 59% and 72% of respondents reported not having a surgical and a medical specialist consultant, respectively. A delayed access to the operating room (OR) of more than 6hours was reported in 31% of cases and access to the OR was reported not to be routinely considered as a priority in 13% of cases. Only 17% of respondents reported that time to transfer to the OR was never a cause for delayed surgery. The main causes for delayed surgery were: delayed diagnosis (45%), delayed validation of surgical intervention (37%), and difficulty of access to the OR (8%). Finally, 83% of respondents estimated that creating dedicated multidisciplinary teams for managing NFs could lead to improving outcomes. CONCLUSION: This survey illustrates the heterogeneous management of NF in French-speaking ICUs and points out several logistical aspects that should be improved to reduce the time to the first surgical debridement.


Subject(s)
Critical Care/methods , Fasciitis, Necrotizing/therapy , Anti-Bacterial Agents/therapeutic use , Delayed Diagnosis , Fasciitis, Necrotizing/drug therapy , Fasciitis, Necrotizing/surgery , France , Health Care Surveys , Humans , Intensive Care Units/statistics & numerical data , Surveys and Questionnaires , Time-to-Treatment
19.
Med Mal Infect ; 44(11-12): 530-4, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25311839

ABSTRACT

OBJECTIVE: We wanted to describe the clinical features associated with urinalysis positive for ESBL-producing Escherichia coli and their impact on antibiotic use. METHODS: We performed a prospective observational study in 13 French hospitals of the Paris area for 3 consecutive months. We included all patients with urine cultures positive for ESBL-producing E. coli. RESULTS: One hundred and seventeen of the 218 patients (54%) presented with asymptomatic bacteriuria, 31 (14%) with cystitis, and 70 (32%) with a parenchymal infection. Nineteen patients with asymptomatic bacteriuria (16%) received antibiotics. Forty-one with parenchymal infections (59%) received a carbapenem. A carbapenem alternative could have been used in every patient treated with a carbapenem, according to antibiotic susceptibility testing results. CONCLUSIONS: Urinary tract infections accounted for 46% of E. coli ESBL positive urinalysis. Fifty percent of parenchymal infections were treated with a carbapenem.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Escherichia coli Infections/urine , Escherichia coli/isolation & purification , Inappropriate Prescribing/statistics & numerical data , Urine/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Proteins/metabolism , Bacteriuria/drug therapy , Catheter-Related Infections/epidemiology , Catheter-Related Infections/microbiology , Child , Child, Preschool , Cross Infection/drug therapy , Escherichia coli/enzymology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Microbial Sensitivity Tests , Middle Aged , Paris , Prospective Studies , Risk Factors , Substrate Specificity , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , Young Adult , beta-Lactam Resistance , beta-Lactamases/metabolism
20.
J Antimicrob Chemother ; 69(9): 2354-60, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24827889

ABSTRACT

BACKGROUND: Legionellosis is a life-threatening disease. The clinical superiority of quinolones or macrolides for treating patients with legionellosis has not been established. METHODS: We performed a systematic review and meta-analysis of studies reporting data that allowed the comparison of quinolones versus macrolides in the treatment of proven legionellosis published from 1 January 1985 to 31 January 2013. We collected baseline aggregate patient characteristics. Studied outcomes included mortality, clinical cure, time to apyrexia, length of hospital stay and occurrence of complications in each treatment group. Treatment effect was assessed using a Mantel-Haenszel random effects model. RESULTS: Among 1005 abstracts reviewed, 12 studies were selected (n=879 patients). No randomized controlled trial was performed directly comparing quinolone and macrolide efficacy in legionellosis. Mean age was 58.3 years, 27.7% were women and Fine score was ≥ 4 in 35.8%. Among 253 patients who received quinolone monotherapy, 10 died (4.0%). Among 211 patients who received macrolide monotherapy, 23 died (10.9%). The pooled OR of death for treatment with a quinolone versus a macrolide was 0.5 (95% CI 0.2-1.3, n=8 studies, 464 patients). Length of stay was significantly shorter in the quinolone monotherapy group. The difference was 3.0 days (95% CI 0.7-5.3, P=0.001, n=3 studies, 263 patients). Neither of two tests for heterogeneity was significant (I (2)=0% for both, P=1). Other studied outcomes were not significantly different among treatment groups. CONCLUSIONS: Few clinical data on legionellosis treatment are available. This first meta-analysis showed a trend toward a lower mortality rate and a significant decrease in length of hospital stay among patients receiving quinolones. These results must be confirmed by a randomized controlled trial.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Legionellosis/drug therapy , Macrolides/therapeutic use , Quinolones/therapeutic use , Humans , Legionellosis/complications , Length of Stay , Survival Analysis , Treatment Outcome
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