Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

Are guidelines on the management of non-tuberculous mycobacteria lung infections respected and what are the consequences for patients? A French retrospective study from 2007 to 2014.

Diagnosis and treatment of lung infections caused by non-tuberculous mycobacteria (NTM) remain challenging. Adherence of the clinicians to the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) 2007 guidelines is often incomplete. Between 2007 and 2014, in Grenoble Alpes University Hospital, France, 132 patients had NTM-positive cultures from lower respiratory tract (LRT) samples. We retrospectively collected diagnosis, treatment, and outcome data of patients, and evaluated the adherence of clinicians to ATS/IDSA guidelines and the consequences of patients' prognoses. Using the ATS/IDSA definitions, 31 out of 132 patients (23.5%) were considered infected, 57 out of 132 patients (43.2%) were considered colonised, 33 out of 132 (25%) were contaminated and 11 (8.4%) had missing data. Among the 31 NTM-infected patients, M. avium (23 out of 31, 74.2%) was most frequently involved. The main risk factor for NTM lung infection was underlying lung disease (30 out of 31, 96.8%). Treatment was not appropriate according to current guidelines in 58.1% of infected patients (18 out of 31). Mainly, the antibiotic treatment was installed based on radiological signs (p = 0.0006), sputum results and bronchoalveolar lavage results (p < 0.0001 and p = 0.003 respectively). Most antibiotic regimens included a macrolide (83.4%). Patients receiving appropriate treatment had the same cure rates as those receiving inappropriate treatment (p = 0.22) and similar relapse rates (p = 0.92). Current medical practices for the treatment of NTM lung infections in our institution are not consistent with the ATS/IDSA guidelines. This could potentially affect the prognosis of these patients and favour the emergence of macrolide resistance in NTM species.

Inventory of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

The objective of this study was to perform an inventory of the extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

Evaluation of an intervention to improve blood culture practices: a cluster randomised trial.

This study aimed to evaluate an intervention to improve blood culture practices. A cluster randomised trial in two parallel groups was performed at the Grenoble University Hospital, France. In October 2009, the results of a practices audit and the guidelines for the optimal use of blood cultures were disseminated to clinical departments. We compared two types of information dissemination: simple presentation or presentation associated with an infectious diseases (ID) specialist intervention. The principal endpoint was blood culture performance measured by the rate of patients having one positive blood culture and the rate of positive blood cultures. The cases of 130 patients in the "ID" group and 119 patients in the "simple presentation" group were audited during the second audit in April 2010. The rate of patients with one positive blood culture increased in both groups (13.62 % vs 9.89 % for the ID group, p = 0.002, 15.90 % vs 13.47 % for the simple presentation group, p = 0.009). The rate of positive blood cultures improved in both groups (6.68 % vs 5.96 % for the ID group, p = 0.003, 6.52 % vs 6.21 % for the simple presentation group, p = 0.017). The blood culture indication was significantly less often specified in the request form in the simple presentation group, while it remained stable in the ID group (p = 0.04). The rate of positive blood cultures and the rate of patients having one positive blood culture improved in both groups. The ID specialist intervention did not have more of an impact on practices than a simple presentation of audit feedback and guidelines.

Appropriateness of blood culture testing parameters in routine practice. Results from a cross-sectional study.

We aimed to assess the appropriateness of routine blood culture testing parameters and antimicrobial therapy for patients with suspected bloodstream infection. We conducted a cross-sectional study of blood cultures registered in the microbiological laboratory at a university-affiliated hospital from 4 to 15 June 2007. Using a structured implicit chart review, two infectious disease specialists assessed the appropriateness of the testing parameters and antimicrobial therapy. Overall, 2,696 blood culture bottles were collected from 260 patients during their stay, including 955 bottles that were evaluated during the study period. The indication of fungal and bacterial blood cultures was rated as appropriate for 75% (95% confidence interval [CI], 65-83) and 91% (95% CI, 87-95) of patients. Only 45% (95% CI, 39-52) of patients had an adequate number of blood cultures (i.e., two to four). An optimal volume of blood (i.e., ≥10 mL) was inoculated in 13% (95% CI, 11-15) of adult bottles. Empirical antimicrobial therapy was appropriate for 60% (95% CI, 43-76) of patients with positive blood cultures. There is room for improvement regarding routine blood culture testing parameters and antimicrobial therapy. The effectiveness of multifaceted interventions in altering the appropriateness of blood culture parameters deserves further research.

[Screening program for tuberculosis among international exchange students in the Department of Isère]. / Dépistage de la tuberculose chez les étudiants étrangers en échange international en Isère.

INTRODUCTION: France is a low-incidence country for tuberculosis (TB). Consequently screening is focused on high-risk populations, in particular migrants. The aim of this study was to evaluate the epidemiology of TB among international exchange students in the Department of Isère and the screening programs used. METHODS: We carried out an organizational audit based on interviews with physicians involved in the management of TB in Isère. We conducted a retrospective descriptive study based on a case series of foreign students treated for TB from 2003 to 2013 inclusively. RESULTS: Forty-six international exchange students were treated for active TB during this time, representing an average incidence of 284/100,000. Two thirds of our studied population were Africans, 72% were asymptomatic at the time of screening. A quarter of our cohort developed TB after the initial screening. Thirty-one cases were confirmed bacteriologically, mainly through bronchoscopy. Outcome (radiological and clinical) on quadruple therapy was satisfactory in all patients. Two patients relapsed, one of them with multi-drug resistant TB. CONCLUSION: Our work confirms that international exchange students are a population at high risk of TB and that screening of this population is essential. The significant number of active TB cases diagnosed after the initial screening stresses the importance of diagnosis and follow up of patients with latent TB infection.

Incidence and prevention of infective endocarditis and bacteraemia after transcatheter aortic valve implantation in a French university hospital: a retrospective study.

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is a rare but severe complication. Among 326 patients who underwent TAVI at Grenoble Alpes University Hospital, six (1.8%) cases of IE and 11 (3.4%) cases of bacteraemia were identified. No cases of IE were linked to the intervention; one was due to Staphylococcus aureus despite a screening and targeted decolonization strategy. This underscores the need for randomized studies to evaluate the benefit and cost-effectiveness of this policy.

A neonatal specialist with recurrent methicillin-resistant Staphylococcus aureus (MRSA) carriage implicated in the transmission of MRSA to newborns.

This study reports an investigation of outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization involving 17 newborns in the neonatal unit of a teaching hospital. A neonatal specialist colonized with MRSA that eventually became mupirocin-resistant was implicated as a recurrent source of transmission of MRSA to newborns.

[Bacillus Calmette-Guérin osteomyelitis. A case report in a former preterm baby]. / Ostéomyélite secondaire à une vaccination par le bacille de Calmette et Guérin : à propos d'un cas chez un ancien prématuré.

Postvaccination osteo-articular mycobacterial infectious disease is a rare and potentially serious complication after Bacillus Calmette-Guérin (BCG) vaccine. We report on a case of a former preterm baby born at 30 weeks of gestation who was vaccinated with BCG Copenhagen strain at 2 months of age. He presented 6 months later with a painful limp, which was found to be a mono-articular osteitis of the right ankle. Histology of the biopsy showed signs of mycobacterial infection and molecular analysis confirmed a BCG infection. Blood tests did not reveal any immunodeficiency associated with the disease (IFN-gamma levels were normal). The course of the disease was favorable with 9 months of antibiotic therapy against mycobacteria. BCG complications should lead to screening for immunodeficiency. The prognosis of BCG osteitis is excellent if the disease is localized. No link between prematurity and BCG complications has been found to date. BCG vaccination of premature infant should be the same as for the general population.

Detection of an outbreak of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in a French hospital.

Staphylococcus aureus isolates were screened for reduced susceptibility to glycopeptides with an initial glycopeptide agar screening test, followed by confirmation of the strains thus identified by two Etest strip techniques and population analysis. This procedure detected 48 methicillin-resistant S. aureus (MRSA) isolates with reduced susceptibility to glycopeptides from 24 patients among 883 MRSA isolates tested. The dissemination of a single clone was confirmed by pulsed-field gel electrophoresis.

[Staphylococcus aureus meningitis with intermediate sensitivity to glycopeptides. Therapeutic indications]. / Méningite à Staphylococcus aureus de sensibilité intermédiaire aux glycopeptides. Implications thérapeutiques

INTRODUCTION: Since 1997, several observations of glycopeptide intermediate Staphylococcus aureus (GISA) infections have been described. We report the case of meningitis. OBSERVATION: A 46 year-old man was treated surgically on several occasions for a meningioma of the back cranial fossa. Intracranial hypertension required the placing of a cerebrospinal leading-catheter. He developed a GISA meningitis. Antibiotics and removal of the catheter cured the infection. DISCUSSION: To our knowledge, this is the first observation of GISA meningitis. Such infections are rare and are probably underestimated due to the lack of standardized detection methods. They occur in fragile, surgical, immunodeficient patients, often living with prostheses. Prior treatment with vancomycine is often reported. The emergence of these infections is a serious therapeutic problem, since vancomycine is a major antibiotic used in the treatment of meticillin-resistant S. aureus (MRSA) infections.

Outcome of central venous catheter-related bacteraemia according to compliance with guidelines: experience with 91 episodes.

BACKGROUND: Infection is a major complication associated with the use of central venous catheters. Guidelines for medical management of catheter-related bacteraemia have been published, but no study has assessed the appropriateness of physician practices. AIM: To assess medical practices in cases of central venous catheter-related bacteraemia (CRB) in a university hospital. METHODS: Cases were recorded over a period of 12 months and their management was evaluated. All cases of positive blood cultures based on central venous catheter sampling were analysed, and episodes of CRB were determined in this group of patients. Medical management and patient outcome were analysed independently by two physicians. FINDINGS: In all, 187 cases of positive blood culture were recorded and 91 cases of CRB were analysed. Systemic antimicrobial therapy was optimal in 56% of the episodes. In 51 episodes, catheter salvage was attempted, for 29 with an indication in agreement with the guidelines but without antibiotic-lock therapy in 20 episodes. The overall medical management was appropriate in 41.8% of the episodes. The overall cure rate was 72.5%. CRB-related death occurred in 5.5% of the episodes. Cure was associated with guideline compliance (P = 0.03) and with adaptation of systemic antimicrobial therapy (P < 0.01). Conservative treatment success was associated with compliance with the guidelines for the indication (P = 0.01). CONCLUSION: Medical management of CRB did not closely adhere to international guidelines. CRB outcome was associated with the appropriateness of this management, particularly when conservative treatment was attempted.

[Pseudomonas aeruginosa and imipenem: correlation between membrane protein D2 and resistance in fifteen strains isolated from patients with mucoviscidosis]. / Pseudomonas aeruginosa et imipénème: corrélation entre protéine de membrane D2 et résistance chez quinze souches isolées de patients mucoviscidosiques.

A characteristic feature of imipenem-resistant strains of Pseudomonas aeruginosa is loss or decreased expression of the outer membrane protein (OMP) D2, whose molecular weight is 45 to 49 kDa. D2 was studied in 15 strains of P. aeruginosa with intermediate susceptibility or resistance to imipenem recovered from the sputum of 15 patients with cystic fibrosis. The OMP was extracted using Sarkosyl and separated by SDS-PAGE electrophoresis. Electrophoresis patterns were compared to those of reference strains 3B and 3C which are resistant and susceptible to imipenem, respectively. Expression of D2 was normal in three strains, weak or very weak in 11 strains and absent in one strain. For 12 strains, the alteration of the D2 protein was consistent with previous reports. However, the finding of normal D2 production in three strains is unusual and suggests the possible presence of another mechanism of resistance.

[Serology of anti-Pseudomonas aeruginosa and mucoviscidosis: diagnostic aid in the differentiation between colonization and infection]. / Sérologie anti-Pseudomonas aeruginosa et mucoviscidose: aide au diagnostic des états de colonisation et d'infection.

Serologic test for Pseudomonas aeruginosa have been found useful for differentiating colonization from infection, especially in chronic disease. A Western blot method was compared with the ELISA used routinely. The Western blot detected serum IgGs against P. aeruginosa outer membrane proteins, whereas the ELISA reacted with IgGs against soluble P. aeruginosa antigens. Among the 103 sera from 58 cystic fibrosis patients studied, all those with ELISA reactivity were positive by Western blot. The antibody response was detected earlier by Western blot than by ELISA, suggesting that the former technique may be useful for the early diagnosis of infection.

[Detection of extended-spectrum beta-lactamases by the rapid ATB E technique. Value of the API V2.1.1 expert system]. / Détection des bêtalactamases a spectre elargi par technique Rapid ATB E. Intérêt du système expert API V2.1.1.

Twenty-two extended-spectrum betalactamase-producing strains of enterobacteriaceae recovered in the authors' hospital were tested using the Rapid ATB E coupled with the API V2.1.1. expert system. The expert system detected 90.9% of ESBL-producing strains. Two strains producing a SHV2 and a CTX1, respectively, escaped detection by the expert system despite concomitant resistance to aminoglycosides.

Effect of D240G substitution in a novel ESBL CTX-M-27.

Escherichia coli clinical strain Gre-1 collected in 2000 from a French hospital harboured a novel CTX-M-encoding gene, designated blaCTX-M-27. CTX-M-27 differed from CTX-M-14 only by the substitution D240G and was the third CTX-M enzyme harbouring this mutation after CTX-M-15 and CTX-M-16. The Gly-240-harbouring enzyme CTX-M-27 conferred to E. coli higher MICs of ceftazidime (MIC, 8 versus 1 mg/L) than did the Asp-240-harbouring CTX-M-14 enzyme. Comparison of CTX-M-14 and CTX-M-27 showed that residue Gly-240 decreased Km for ceftazidime (205 versus 940 microM), but decreased hydrolytic activity against good substrates, such as cefotaxime (kcat, 113 versus 415 s-1), probably owing to the alteration of beta3 strand positioning during the catalytic process.

A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate.

Escherichia coli GR102 was isolated from feces of a leukemic patient. It expressed different levels of resistance to amoxicillin or ticarcillin plus clavulanate and to the various cephalosporins tested. The double-disk synergy test was weakly positive. Production of a beta-lactamase with a pI of 5.6 was transferred to E. coli HB101 by conjugation. The nucleotide sequence was determined by direct sequencing of the amplification products obtained by PCR performed with TEM gene primers. This enzyme differed from TEM-1 (blaT-1B gene) by four amino acid substitutions: Met-->Leu-69, Glu-->Lys-104, Gly-->Ser-238 and Asn-->Asp-276. The amino acid susbstitutions Leu-69 and Asp-276 are known to be responsible for inhibitor resistance of the IRT-4 mutant, as are Lys-104 and Ser-238 substitutions for hydrolytic activity of the extended-spectrum beta-lactamases TEM-15, TEM-4, and TEM-3. These combined mutations led to a mutant enzyme which conferred a level of resistance to coamoxiclav (MIC, 64 microg/ml) much lower than that conferred by IRT-4 (MIC, 2,048 microg/ml) but higher than that conferred by TEM-15 or TEM-1 (MIC, 16 microg/ml). In addition, the MIC of ceftazidime for E. coli transconjugant GR202 (1 microg/ml) was lower than that for E. coli TEM-15 (16 microg/ml) and higher than that for E. coli IRT-4 or TEM-1 (0.06 microg/ml). The MICs observed for this TEM-type enzyme were related to the kinetic constants Km and k(cat) and the 50% inhibitory concentration, which were intermediate between those observed for IRT-4 and TEM-15. In conclusion, this new type of complex mutant derived from TEM-1 (CMT-1) is able to confer resistance at a very low level to inhibitors and at a low level to extended-spectrum cephalosporins. CMT-1 received the designation TEM-50.

[Bacillary angiomatosis related to Rochalimaea quintana. Anatomoclinical and ultrastructural study of cutaneous localizations in AIDS]. / Angiomatose bacillaire liée à Rochalimaea quintana. Etude anatomoclinique et ultrastructurale de localisations cutanées au cours d'un SIDA.

We report a case of bacillary angiomatosis in a 53-year-old homosexual man with acquired immunodeficiency syndrome (AIDS). Pathological and bacteriological studies of cutaneous nodules led to the identification of a rickettsia: Rochalimaea quintana. This observation prompted us to relate the clinical presentation of cutaneous and visceral forms of this disease. Histopathological patterns are also considered. They usually consist in a lobular proliferation of capillaries with plump and sometimes epithelioid endothelial cells. Polymorphonuclear cells, histiocytes and necrotic areas may be present. The most characteristic feature is the presence of interstitial, granular and amorphous clusters of bacteria. Diagnostic problems can be raised with Kaposi's angiosarcoma which can be associated with bacillary angiomatosis. Two types of Rochalimaea have so far been isolated in this disease i.e., R. henselae which is the most frequently involved, and R. quintana. The usefulness of making such a diagnosis resides in the sensitivity of bacillary angiomatosis to antibiotics, emphasing the need to carefully look for the presence of bacterial clusters when atypical angioproliferative lesion appears in patients with AIDS.