B. Fantin

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 French Gaucher’s disease registry: clinical characteristics, complications and treatment of 562 patients

BackgroundClinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.MethodsAll patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.ResultsAmong the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%).ConclusionThis registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.

Two Cases of Cerebral Aspergillosis Successfully Treated with Voriconazole

Described here are two cases of cerebral aspergillosis successfully treated with voriconazole after the failure of first-line treatment with amphotericin B deoxycholate. In both cases, clinical and radiological cure was achieved within 6 weeks. Voriconazole should be considered as first-line therapy for cerebral aspergillosis.

Diversity of Individual Dynamic Patterns of Emergence of Resistance to Quinolones in Escherichia coli From the Fecal Flora of Healthy Volunteers Exposed to Ciprofloxacin

BACKGROUND Emergence of quinolone-resistant Escherichia coli (QREC) is an increasing clinical challenge mostly originating in fecal microbiota. The dynamics of the emergence of QREC in feces from individuals exposed to ciprofloxacin is unknown. METHODS A total of 48 healthy volunteers received oral ciprofloxacin for 14 days. Fecal specimens were collected on days 0, 8, 14, and 42. Subpopulations of QREC were detected on selective agar, genetically characterized, and compared with quinolone-susceptible E. coli (QSEC) strains collected on different days. RESULTS On day 42, 34 subjects carried QSEC, and 14 carried QREC. Of the 14 who carried QREC, 9 carried quinolone-susceptible E. coli on day 0, 1 carried E. coli with a lower level of quinolone resistance on day 0, and 4 carried E. coli with similar levels of resistance and RAPD-genotypes on days 0 and 42. No plasmid acquisition and no selection of resistant mutants from the initial microbiota was evidenced in any case. CONCLUSIONS In QREC emerging under ciprofloxacin pressure in the fecal microbiota, no proof of selection of quinolone-resistant mutants from the initial microbiota was evidenced, suggesting that QREC strains on day 42 were either present at undetectable levels in the initial microbiota or that exogenous acquisition of QREC strains occurred. Clinical Trials Registration. NCT00190151.

Independent Behavior of Commensal Flora for Carriage of Fluoroquinolone-Resistant Bacteria in Patients at Admission

ABSTRACT The important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting Escherichia coli in the fecal flora, coagulase-negative Staphylococcus (CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in E. coli, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal E. coli (i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [http://clinicaltrials.gov/ct2/show/NCT00520715 ]).

Expression of Glycopeptide-Resistance Gene in Response to Vancomycin and Teicoplanin in the Cardiac Vegetations of Rabbits Infected with VanB-Type Enterococcus faecalis

VanB-type resistance in enterococci corresponds to resistance to vancomycin but not to resistance to the related glycopeptide teicoplanin, because the vanB gene cluster is activated by the VanR(B)-VanS(B) 2-component regulatory system in response to vancomycin but not to teicoplanin. Mutations in the vanS(B) gene allow for constitutive or teicoplanin-inducible expression of the resistance genes. To analyze in vivo expression of the van genes in rabbits with experimental endocarditis, a VanB-type Enterococcus faecalis with a transcriptional fusion between the P(YB) promoter of resistance genes and the gfpmut1 gene for the green-fluorescent protein in the chromosome was constructed. Rounded heaps containing fluorescent bacteria were detected in vegetation slides from rabbits treated with vancomycin but not in those from control rabbits, revealing induction of a tightly regulated vanB gene cluster. Teicoplanin-resistant mutants were detected as fluorescent bacteria in rabbits treated with teicoplanin. Thus, the reporter system monitored expression of a glycopeptide-resistance gene in vivo at a single-cell level.

Activity of temocillin in a murine model of urinary tract infection due to Escherichia coli producing or not producing the ESBL CTX-M-15

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.

Comparative dynamics of the emergence of fluoroquinolone resistance in staphylococci from the nasal microbiota of patients treated with fluoroquinolones according to their environment

Fluoroquinolone-resistant staphylococci (FQRS) are primarily selected in the nasal microbiota during fluoroquinolone (FQ) treatment. To gain insight into the dynamics of the emergence of FQRS, 49 hospitalised patients (HPs) and 62 community patients (CPs) treated with FQs were studied. Nasal swabs were collected before (T0), at the end of (T1) and 1 month after (T2) FQ treatment. FQRS were identified by mass spectrometry. Antibiotic resistance was determined. Pre- and post-exposure staphylococci populations were compared phenotypically and by MLST to determine the origin of FQRS. At T0, 33/49 HPs (67%) and 24/62 CPs (39%) carried FQRS (OR=3.3, 95% CI: 1.4-7.9; P<0.001). Among patients with no FQRS at T0, 15/16 HPs (94%) and 16/38 CPs (42%) had FQRS detected at T1 and/or T2 (OR=19.6, 95% CI: 2.5-902; P<0.001). Among FQRS having emerged, co-resistance to meticillin was detected in 87% and 82% of HPs and CPs, respectively. No selection of resistance emerging from the initial microbiota was evidenced. FQRS showed decreased species diversity in favour of Staphylococcus haemolyticus and Staphylococcus epidermidis. As a consequence of FQ treatment, acquisition of FQRS in the nasal microbiota is frequent in the community and almost inevitable in hospitals. Acquisition from extranasal sites prevails. A restriction in species diversity in favour of more pathogenic and resistant species occurs. This highlights the major impact of FQ treatment on nasal microbiota, the role of the ecological environment in the emergence of FQRS, and the high-risk of dissemination of resistant staphylococci.

Acute respiratory failure due to diaphragmatic weakness revealing a polymyositis

Of the different respiratory disorders that complicate the course of polymyositis, diaphragmatic weakness is one that is seldom described and most often suspected rather than confirmed. We report a case of severe diaphragmatic weakness as a cause of acute respiratory failure revealing a polymyositis. The diaphragmatic involvement was proven by a very low esophageal pressure in response to cervical magnetic stimulation of the phrenic nerve. Corticosteroids and intravenous gammaglobulin, combined with mechanical ventilation, achieved a progressive recovery of diaphragmatic weakness.

Recurrent valvular replacement due to exacerbation of Behcet’s disease by Streptococcus agalactiae infection

Valvular heart complications in Behcets disease are rarely reported. Moreover, the risk of dehiscence in postoperative valvular replacement is high in Behcets disease. We report a case of recurrent aortic prosthetic dehiscence revealing Behcets disease in a young woman. Each disease exacerbation was concomitant to a Streptococcus agalactiae infection. This infection appears to act as a trigger for Behcets disease exacerbation. The patient was successfully treated with immunosuppression plus antibiotic therapy.