Integrating rapid diagnostics in Gram-negative bloodstream infections of patients colonized by carbapenemase-producing Enterobacterales.

We implemented a fast-track diagnostic approach for Gram-negative bloodstram infections (BSIs) among carbapenemase-producing Enterobacterales (CPE) carriers. Within a large cohort of patients with CPE rectal carriage, 18.1% developed Gram-negative BSIs, of which 69.5% were caused by CPE. Direct matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis provided reliable identification in 97% and 53.8% of monomicrobical blood cultures positive to Enterobacterales and non-fermenting Gram-negative species, respectively. Overall, sensitivity and specificity of NG-Test Carba 5 compared with the composite reference method after discrepant analysis were 100%, in polimicrobial blood cultures too. The combined use of direct MALDI-TOF MS and NG-Test Carba 5 assay might be a reliable and cost-effective tool for accelerating the laboratory diagnosis of CPE BSI in cohorts of high-risk patients such as CPE carriers.

Ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in KPC-producing Klebsiella pneumoniae infections: A case series.

OBJECTIVES: Since the introduction of the ß-lactam/ß-lactamase inhibitor ceftazidime-avibactam (CZA), rapid evolution of resistance has been reported in different KPC-producing Klebsiella pneumoniae isolates. In this multicenter retrospective study, we describe the emergence of CZA resistance and evaluate the mutations that might be responsible for the restoration of carbapenem susceptibility. METHODS: During a study period of 18 months, KPC-producing K. pneumoniae isolates of five hospitalized patients were collected with phenotypic development of CZA resistance. RESULTS: In vitro restoration of carbapenem susceptibility during treatment was observed in 3 isolates. Whole genome sequencing of these isolates showed a D179Y mutation in the KPC gene of 2 variants and a KPC-2 with a Δ242-GT-243 deletion (KPC-14). Two KPC-3 variants showed CZA resistance with sustained carbapenemase activity without genomic adaptations in the KPC gene. CONCLUSIONS: This study confirms the emergence of CZA resistance in KPC K. pneumoniae. The role of carbapenems in treating patients with these variants is unclear and combination therapies warrant further investigation.

RESIST-5 O.O.K.N.V. and NG-Test Carba 5 assays for the rapid detection of carbapenemase-producing Enterobacterales from positive blood cultures: a comparative study.

We prospectively compared the performance of RESIST-5 O.O.K.N.V. and NG-Test Carba 5 assays directly from blood cultures spiked with 130 characterized Enterobacterales isolates. Overall, both assays yielded 100% sensitivity to detect KPC-type carbapenemases and OXA-48-like carbapenemases. Both assays failed to detect KPC-31 and KPC-33, D179Y point mutation variants of KPC-3 and KPC-2, that are deprived of carbapenemase activity and confer resistance to ceftazidime-avibactam. On blood culture bacterial pellets, NDM- and VIM-type carbapenemases were detected in 50.0% and 52.2%, respectively, by RESIST-5 O.O.K.N.V. vs 100% by NG-Test Carba 5. The sensitivity of RESIST-5 O.O.K.N.V. improved to 100% and 95.6%, respectively, by performing the assay on 4-h early subculture.

Accuracy of the ELITe MGB assays for the detection of carbapenemases, CTX-M, Staphylococcus aureus and mecA/C genes directly from respiratory samples.

INTRODUCTION: Bacterial lower respiratory tract infections (BLRTI) may represent serious clinical conditions which can lead to respiratory failure, intensive care unit admission and high hospital costs. The detection of carbapenemase- and extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales, as well as meticillin-resistant Staphylococcus aureus (MRSA), has become a major issue, especially in healthcare-associated infections. This study aimed to determine whether molecular assays could detect genes encoding carbapenemases, ESBL and MRSA directly from respiratory samples in order to expedite appropriate therapy and infection control for patients with BLRTI. METHODS: The carbapenem-resistant enterobacterales (CRE), ESBL and MRSA/SA ELITe MGB assays were performed directly on 354 respiratory specimens sampled from 318 patients admitted with BLRTI. Molecular results were compared with routine culture-based diagnostics results. RESULTS: Positive (PPV) and negative (NPV) predictive values of the CRE ELITe MGB kit were 75.9% [95% confidence interval (CI) 60.3-86.7] and 100%, respectively. PPV and NPV of the ESBL ELITe MGB kit were 80.8% (95% CI 63.6-91.0) and 99.1% (95% CI 96.6-99.8), respectively. PPV and NPV of the MRSA/SA ELITe MGB kit were 91.7% (95% CI 73.7-97.7)/100% and 98.3% (95% CI 89.8-99.3)/96.8% (95% CI 81.6-99.5), respectively. DISCUSSION: Validity assessment of molecular assays detecting the main antibiotic resistance genes directly from respiratory samples showed high accuracy compared with culture-based results. Molecular assays detecting the main carbapenemase, ESBL, S. aureus and meticillin resistance encoding genes provide an interesting tool with potential to expedite optimization of antibiotic therapy and infection control practices in patients with BLRTI.

Detection of antibiotic resistance genes from blood cultures: performance assessment and potential impact on antibiotic therapy management.

Molecular assays may constitute a valid method for timely prediction of antimicrobial resistance and optimization of empirical antibiotic therapies. This study assessed ELITe MGB assays of blood cultures to detect the main carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, Staphylococcus aureus and mec genes in less than 3 h. Excellent agreement was found between the results of genotypic and conventional phenotypic approaches. Retrospective analysis of medical records revealed that approximately 50% of bloodstream infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae or meticillin-resistant S. aureus were initially treated with inactive drugs. Overall, 36.3% of patients could have been treated with appropriate therapy at least 24 h earlier if molecular data had been used.

Propylthiouracil induced pulmonary-renal syndrome: a case report.

Propylthiouracil (PTU) is known to induce antineutrophil cytoplasmatic antibody (ANCA) seropositivity; however, small vessel vasculitis (SVV) with pulmonary and renal involvement is rare. We present the case of an 81-year-old woman on PTU treatment due to toxic nodular goitre who developed alveolar hemorrhage and rapidly progressive glomerulonephritis. The authors highlight the importance of early recognising drug-induced pulmonary-renal syndrome (PRS) in order to avoid unnecessary tests, a delay in the diagnosis and evolution to end-stage kidney disease or life-threatening conditions.

Shock following subcutaneous injections of polymethyl methacrylate

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