Antibiotic resistance plasmids cointegrated into a megaplasmid harbouring the blaOXA-427 carbapenemase gene

OXA-427 is a new class-D carbapenemase encountered in different species of Enterobacteriaceae in a Belgian hospital. To study the dispersal of this gene, we describe the comparative analysis of two plasmids containing the blaOXA-427 gene isolated from a Klebsiella pneumoniae and an Enterobacter cloacae complex strain. The two IncA/C2 plasmids containing blaOXA-427 share the same backbone, however, in the K. pneumoniae this plasmid is cointegrated into an IncFIB plasmid forming a 321 kb megaplasmid with multiple multi-resistance regions

How to: interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST)

BACKGROUND: EUCAST has revised the definition of the susceptibility category "I" from "Intermediate" to "Susceptible, Increased exposure". This implies that "I" can be used where the drug-concentration at the site of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, "I" is no longer used as a buffer-zone to prevent technical fact

Broad-Range PCR Coupled with Electrospray Ionization Time of Flight Mass Spectrometry for Detection of Bacteremia and Fungemia in Patients with Neutropenic Fever

Infection is an important complication in patients with hematologic malignancies or solid tumors undergoing intensive cytotoxic chemotherapy. In only 20 to 30% of the febrile neutropenic episodes, an infectious agent is detected by conventional cultures. In this prospective study, the performance of broad-range PCR coupled with electrospray ionization time of flight mass spectrometry (PCR/ESI-MS) technology was compared to conventional blood cultures (BC) in a consecutive series of samples from high-risk hematology patients. In 74 patients, BC and a whole-blood sample for PCR/ESI-MS (Iridica BAC BSI; Abbott, Carlsbad, CA, USA) were collected at the start of each febrile neutropenic episode and, in case of persistent fever, also at day 5. During 100 different febrile episodes, 105 blood samples were collected and analyzed by PCR/ESI-MS. There was evidence of a bloodstream infection (BSI) in 36/105 cases (34%), based on 14 cases with both PCR/ESI-MS and BC positivity, 17 cases with BC positivity only, and 5 cases with PCR/ESI-MS positivity only. The sensitivity of PCR/ESI-MS was 45%, specificity was 93%, and the negative predictive value was 80% compared to blood culture. PCR/ESI-MS detected definite pathogens (Fusobacterium nucleatum and Streptococcus pneumoniae) missed by BC, whereas it missed both Gram-negative and Gram-positive organisms detected by BC. PCR/ESI-MS testing detected additional microorganisms but showed a low sensitivity (45%) compared to BC in neutropenic patients. Our results indicate a lower concordance between BC and PCR/ESI-MS in the neutropenic population than what has been previously reported in other patient groups with normal white blood cell distribution, and a lower sensitivity than other PCR-based methods.status: publishe

Clinical impact of PCR-based Aspergillus and azole resistance detection in invasive aspergillosis. A prospective multicenter study

BACKGROUND: Invasive aspergillosis(IA) by a triazole resistant Aspergillus fumigatus is associated with a high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. METHODS: In a prospective study in the Netherlands and Belgium, we evaluated the clinical value of the multiplex AsperGenius®PCR in hematology patients from 12 centers. This PCR detects the most frequent cyp51A mutations in A. fumigatus conferring azole-resistance. Patients were included when a CT-scan showed a pulmonary infiltrate and bronchoalveolar lavage(BALf) sampling was performed. The primary endpoint was antifungal treatment failure in patients with azole-resistant IA. Patients with mixed azole-susceptible/resistant infections were excluded. RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available in 276/323(94%) and probable IA diagnosed in 99/276(36%). Sufficient BALf for PCR testing was available in 293/323(91%). Aspergillus DNA was detected in 116/293(40%) and A.fumigatus DNA in 89/293(30%). The resistance PCR was conclusive in 58/89(65%) and resistance detected in 8/58(14%). Two had a mixed azole-susceptible/resistant infection. In the 6 remaining patients, treatment failure was observed in one. Galactomannan positivity was associated with higher mortality(p=0.004). In contrast, mortality of patients with an isolated positive Aspergillus PCR was comparable to those with a negative PCR(p=0.83). CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (e.g. minimum Ct-value and/or PCR positive on >1 BALf sample)

A Global Declaration on Appropriate Use of Antimicrobial Agents across the Surgical Pathway

This declaration, signed by an interdisciplinary task force of 234 experts from 83 different countries with different backgrounds, highlights the threat posed by antimicrobial resistance and the need for appropriate use of antibiotic agents and antifungal agents in hospitals worldwide especially focusing on surgical infections. As such, it is our intent to raise awareness among healthcare workers and improve antimicrobial prescribing. To facilitate its dissemination, the declaration was translated in different languages