J. Leroy

Quantitative Polymerase Chain Reaction Detection of Circulating DNA in Serum for Early Diagnosis of Mucormycosis in Immunocompromised Patients

BACKGROUND The aim of our study was to assess the detection of circulating DNA from the most common species of Mucorales for early diagnosis of mucormycosis in at-risk patients. METHODS We retrospectively evaluated a combination of 3 quantitative polymerase chain reaction (qPCR) assays using hydrolysis probes targeting Mucor/Rhizopus, Lichtheimia (formerly Absidia), and Rhizomucor for circulating Mucorales detection. Serial serum samples from 10 patients diagnosed with proven mucormycosis (2-9 samples per patient) were analyzed. RESULTS No cross-reactivity was detected in the 3 qPCR assays using 19 reference strains of opportunistic fungi, and the limit of detection ranged from 3.7 to 15 femtograms/10 µL, depending on the species. DNA from Mucorales was detected in the serum of 9 of 10 patients between 68 and 3 days before mucormycosis diagnosis was confirmed by histopathological examination and/or positive culture. All the qPCR results were concordant with culture and/or PCR-based identification of the causing agents in tissue (Lichtheimia species, Rhizomucor species, and Mucor/Rhizopus species in 4, 3, and 2 patients, respectively). Quantitative PCR was negative in only 1 patient with proven disseminated mucormycosis caused by Lichtheimia species. CONCLUSION Our study suggests that using specific qPCR targeting several species of Mucorales according to local ecology to screen at-risk patients could be useful in a clinical setting. The cost and efficacy of this strategy should be evaluated. However, given the human and economic cost of mucormycosis and the need for rapid diagnosis to initiate prompt directed antifungal therapy, this strategy could be highly attractive.

Haemophilus influenzae Carriage in Children Attending French Day Care Centers: a Molecular Epidemiological Study

ABSTRACT The nasopharyngeal Haemophilus influenzae flora of healthy children under the age of 3 years attending day care centers in three distinct French geographic areas was analyzed by sampling during two periods, spring 1999 (May and June) and fall 1999 (November and December). The average carrier rate among 1,683 children was 40.9%. The prevalence of capsulated H. influenzae carriers was 0.4% for type f and 0.6% for type e. No type b strains were found among these children, of whom 98.5% had received one or more doses of anti-Haemophilus b vaccine. Among the strains, 44.5% were TEM-type beta-lactamase producers and nine (1.3%) were beta-lactamase-negative ampicillin-resistant strains. Pulsed-field gel electrophoresis restriction patterns showed a large diversity with 366 SmaI patterns from 663 strains. Among the strains isolated during a given period, 33% were isolated simultaneously in more than one area. In each area, depending on the sampling period, 68 to 72% of the strains had new pulsotypes and persistence of 28 to 32% of the strains was noted. For the 297 beta-lactamase-producing strains, 194 patterns were found. The genomic diversity of these strains was comparable to that of the whole set of strains and does not suggest a clonal diffusion. Among the beta-lactamase-producing strains isolated in November and December, depending on the area, 66 to 73% had new pulsotypes with persistence of only 27 to 33% of the strains. In any given geographic area, colonization by H. influenzae appears to be a dynamic process involving a high degree of genomic heterogeneity among the noncapsulated colonizing strains.

Alternatives to carbapenems in ESBL-producing Escherichia coli infections

OBJECTIVES The authors had for objective to assess the activity of a wide panel of antibiotics on extended-spectrum-β-lactamase producing Escherichia coli isolates (ESBL-Ec), because of the sharp increase of their frequency, leading to an increased use of carbapenems. MATERIAL AND METHODS We selected 100 ESBL-Ec in which ESBLs were identified by PCR and sequencing, between 2009 and 2010. We determined the MICs of amoxicillin-clavulanate, piperacillin-tazobactam, temocillin, mecillinam, cefoxitin, cefotaxime, ceftazidime, aztreonam, tigecycline, nitrofurantoin, and fosfomycin using reference methods. The susceptibility profiles were defined according to EUCAST 2012 recommendations. RESULTS Fosfomycin, nitrofurantoin, and pivmecillinam were active against more than 90% of isolates and remain excellent choices for the oral treatment of urinary tract infections (UTIs). Temocillin and piperacillin-tazobactam are also good candidates for the treatment of pyelonephritis or bloodstream infections. Only 27, 23, and 8% of isolates were susceptible to ceftazidime, cefepime, and cefotaxime, respectively. CONCLUSION Our study results prove that in many cases, there are non-carbapenem alternatives for the treatment of ESBL-Ec infections.

Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement

ABSTRACT Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array–high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.

Antibiotic prescription in nursing homes for dependent elderly people: a cross-sectional study in Franche-Comté.

OBJECTIVES We had for objective to determine the rate of patients treated with antibiotics and the determinants of antibiotic stewardship in nursing homes for dependent elderly people (French acronym EHPAD), of a French region (Franche-Comté). PATIENTS AND METHODS A representative sample of EHPAD, in Franche-Comté, was included in a cross-sectional study made between April and June 2012. An external auditor and the EHPAD head physician collected data on the facility and on residents receiving antibiotics on the study day. An infectious diseases specialist and an infection control practitioner analyzed each prescription, a posteriori, to assess criteria of antimicrobial stewardship including re-assessment of the prescription between 48 and 72h after initiation of antibiotic treatment. RESULTS Sixty-one (2.76%) of the 2210 residents in 18 nursing homes were under antibiotic treatment. This rate ranged from 0% to 7.5% among nursing homes. Sixty-two percent of prescriptions complied with recommendations regarding the choice of the drug, and 41.5% could not be improved by choosing an agent with a weaker ecological impact. Globally, 17.8% of prescriptions met all stewardship criteria including re-assessment of the prescription between 48 and 72h after initiation of antibiotic treatment. CONCLUSIONS The study results differed. The rate of antibiotic prescription was low in Franche-Comté EHPAD compared to available European data, but antibiotic therapy could be greatly improved. This stresses the need to better train EHPAD physicians for antibiotic stewardship.

Évaluation de la prescription antibiotique dans un centre hospitalier universitaire français

OBJECTIVE The aim of this study was to evaluate antibiotic prescription in a French university hospital. DESIGN Our hospital participated in an international European Surveillance of Antimicrobial Consumption (ESAC) project study, including a longitudinal survey of monthly antibiotic use between 1998 and 2005, and a point prevalence study in 2006. All patients in the hospital on the day of survey were included in the study. Antibiotic treatments were assessed according to local antibiotic guidelines. RESULTS Between 1998 and 2005, antibiotic use increased from 551.9 to 628.5 defined daily doses per 1000 patient-days. This increase was linked to the increase of penicillin and fluoroquinolone consumption. In the point prevalence survey, 251 (27.0%) of the 930 included patients received one or several antibiotics for a total of 395 antibiotic prescriptions. Community-acquired infections were the first indication of treatment (41.8% of prescriptions), hospital-acquired infections accounted for 34.9% of prescriptions, surgical and medical antibiotic prophylaxis for 22.4%. The assessment of antibiotic prescriptions showed that 73.7% of them were in conformity with local recommendations. CONCLUSIONS This type of study is relevant to identify critical points of inadequate antibiotic use so as to suggest corrective measures to prescribers.

Surgical antibiotic prophylaxis compliance in a university hospital

OBJECTIVE To assess surgical antibiotic prophylaxis (SAP) practices in a university hospital in order to identify risk factors associated with non-compliance. STUDY DESIGN Retrospective monocentric study conducted over a 4-month period. PATIENTS AND METHODS Data were collected from the software used in the operating theatre. Practice non-compliance was evaluated in comparison with the 2010 version of the French national recommendations. We only took in account the interventions identified as priority surveillance interventions according to the surgical site infections national surveillance. The risk factors associated with SAP non-compliance were identified with a multivariate statistical analysis. RESULTS We evaluated 1312 SAPs. Among the 1298 indicated SAPs, 44.4% were not compliant. The most frequent inappropriate criterion was the timing of injection (34.8% non-compliance), which was, in the majority of cases, too close to the time of incision. Other inappropriate criteria were identified: antibiotic choice for patients allergic to β-lactams (inappropriate among 45% of allergic patients), and antibiotic dosing for obese patients (96% of non-compliance). Obesity (OR=84.32), allergy to β-lactams (OR=17.11) and certain types of surgery (digestive, OR=4.56; gynaecological and obstetrical, OR=7.10; urological, OR=3.95) were independently associated with the non-compliance of SAP practices. CONCLUSION Improvement measures that target the timing of injection, obese or allergic patients are necessary.

Identifying Patients Harboring Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae on Hospital Admission Is Not That Simple

We read with interest the paper by Mario Tumbarello et al. ([3][1]), and we agree with the authors that identification of the patients at high risk of infection with extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is a key issue. Their identification of patients at high

Impact d'un guide régional pour la prise en charge des infections urinaires sur les pratiques d'antibiothérapies

AIM AND METHOD We assessed the impact of a committed guideline at the end of the first quarter 2008 on the management of urinary tract infection (UTI) with antibiotic prescription (fluoroquinolone, fosfomycin, and nitrofurantoin), by analysing reimbursement data for ambulatory care provided by the regional health insurance agency. RESULTS During the survey, we observed a 13.2% decrease of norfloxacin prescriptions between the first quarter 2008 and the first quarter 2009. The (fosfomycin+nitrofurantoin)/norfloxacin ratio increased between the third quarter 2007 and the first quarter 2009 from 0.55 to 0.72 and from 0.82 to 1.13 for general practitioners and hospital physicians respectively. The global number of patients treated with these antibiotics remained stable during the period. The number of fluoroquinolone prescription was stable between the first quarter 2008 and the first quarter 2009 with 28,427 DDD and 28,363 DDD, respectively; while the number of single dose rise in the same time from 151 DDD to 427.5 DDD, respectively. DISCUSSION The three messages which seem to be essential for an optimal use of fluoroquinolones in UTIs are: no treatment for bacterial colonisation (asymptomatic bacteriuria) except for specific cases, no indication for fluoroquinolones in non-complicated acute cystitis and for elderly women, UTI is complicated only if it occurs in women with co-morbidities regardless of age. CONCLUSION Our indicators suggest that our guideline had an impact on the prescription of fluoroquinolones for uncomplicated acute cystitis.

Short-course treatment with ceftriaxone for leptospirosis: A retrospective study in a single center in Eastern France

Short-course (less than 7 days) antibiotic treatments have been rarely assessed in the management of leptospirosis. We analyzed the charts of patients hospitalized with confirmed and probable leptospirosis in a teaching hospital between 1994 and 2012. Of 89 patients with confirmed or probable leptospirosis, 21 patients (11 confirmed, 10 probable - 14 uncomplicated and 7 severe forms) admitted between 2001 and 2012 received ceftriaxone (1-2 g daily) for less than 7 days. Apyrexia was obtained within 2 days of treatment in all patients and no relapse was observed. These data support the hypothesis that short-course treatments of 3-6 days with ceftriaxone (1-2 g per day) may be an option in the treatment of uncomplicated and severe forms of leptospirosis responding quickly to therapy. This hypothesis deserves being confirmed in further clinical studies.