Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

BACKGROUND: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center. METHODS: Blood and tissue culture results collected between January 2005 and January 2018 and maintained in the microbiology laboratory database at the Cleveland Clinic were reviewed to identify those with C. septicum reported. Each was reviewed to determine radiographic or histopathologic correlation with aortic disease. RESULTS: Seven cases of C. septicum aortitis were reviewed. Underlying malignant disease was found in four cases and a history of remote malignant disease in one case. The most common location for infection was the infrarenal abdominal aorta. Vascular surgery had previously been performed in three of the cases. Five of the seven patients underwent operative repair. All patients were treated with ß-lactam antibiotics. The two patients who did not undergo an operation died, which is consistent with the 100% mortality described in the literature. Of the five patients who underwent an operation, there was only one documented survivor and one was lost to follow-up. CONCLUSIONS: In the largest reported case series, only a small percentage of patients with C. septicum-infected aortic aneurysms survived >1 year. In the patients described, those who did not receive an operation had 100% mortality. Earlier recognition and prompt operation with appropriate antimicrobial therapy are needed to improve the outcome of patients diagnosed with this rare infection.

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

Prospective Evaluation of Molecular Assays for Diagnosis of Vaginitis.

Molecular tests to diagnose conditions involving the disruption of normal microbiota are difficult to optimize. Using Nugent-scored Gram stain (NS) as the reference standard, we evaluated the performance of 3 molecular assays for the diagnosis of bacterial vaginosis (BV) and examined the impact of an incremental increase in bacterial targets. The BD Affirm assay includes a DNA probe for Gardnerella vaginalis, the Hologic transcription-mediated amplification (TMA) analyte-specific reagent (ASR) assay adds a second Lactobacillus sp. target, and the recently cleared in vitro diagnostic use (IVD) Aptima BV assay includes a third target (Atopobium vaginae). The diagnosis of vulvovaginal candidiasis (VVC) by the Affirm and Candida vaginitis Hologic TMA ASR assays was assessed using microscopy for yeast as the reference standard. From May to December 2018, 111 women with vaginitis symptoms prompting the clinician to order an Affirm test were enrolled with informed consent for the collection of additional specimens. Clinicians accurately predicted BV as the most likely diagnosis for 71% of the 45 patients with BV. Coinfection occurred in 13.5% of patients. For BV, the specificity of the Aptima IVD assay (86.3%) was higher than the Affirm assay (60.6%, P = 0.0002), but sensitivities were not significantly different. For VVC, the sensitivity of the ASR assay (100%) was higher than Affirm (75.9%; P = 0.023) and the specificity of the Affirm assay (98.8%) was higher than the ASR assay (86.6%; P = 0.004).

Multicenter Evaluation of a Gradient Diffusion Method for Antimicrobial Susceptibility Testing of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with peptic ulcer disease, dyspepsia, and gastric malignancy. Antimicrobial susceptibility testing (AST) is often requested for patients who fail eradication therapy. The Clinical and Laboratory Standards Institute (CLSI) reference method, agar dilution (AD), is not performed in most laboratories and maintaining organism viability during transit to a reference laboratory is difficult. We assessed the performance of the Etest (bioMérieux) as a method for H. pylori AST in comparison to AD. Etest MICs were determined for 83 H. pylori isolates at ARUP and Cleveland Clinic (CC). Categorical agreement (CA), very major, major, and minor errors (VME, ME, and mE) were determined for Etest using AD performed at Mayo Clinic Laboratories as the reference method. Testing on isolates with errors was repeated to determine final results summarized below. For clarithromycin, 66.3% of isolates were resistant (R) by AD; Etest results at each laboratory showed 1mE (1.2%) and 1 ME (3.8%). For tetracycline, only 2 isolates were R by AD; a single VME occurred at both sites (98.8% CA, 50% VME) with the same isolate. Applying EUCAST levofloxacin breakpoints to interpret ciprofloxacin results, 60.2% of isolates were R by AD; ARUP CA was 97.6% (1 ME (3%), 1 VME (2%)) and CC CA was 96.3% (1 ME (3%), 2 VMEs (4%)). Despite high error rates, the categorical agreement was acceptable (>90%) for all three antibiotics between AD and Etest. In-house susceptibility testing by gradient diffusion can allow for testing of fastidious organisms that may not survive transport to specialized laboratories; however, the method is not without technical challenges. Characterization of resistance mechanisms, increased AD dilutions, and testing from the same inoculum may determine if the observed errors reflect technical issues or breakpoints that need optimization. IMPORTANCE Routine antimicrobial susceptibility testing (AST) of Helicobacter pylori by agar dilution is difficult to perform and not practical in most clinical microbiology laboratories. The Etest gradient diffusion method can be a reliable alternative for H. pylori AST with the advantage of being a less laborious quantitative method. This work reveals that an optimized Etest method can provide acceptable performance for H. pylori AST and describes the challenges associated with this methodology.

Commercial Licensing of HIV-1 Protease: Applications of the NIH Research Tools Policy.

Licensing of the HIV-1 protease gene by the NIH Office of Technology Transfer (OTT) provides an example of the effective use of the principles of the NIH Research Tools Policy, which was designed to provide broad access to important biomedical technologies. The OTT licensing experience is presented in detail as it was applied to research reagents, diagnostics and drug development to thus enhance the overall development process for a wide variety of medical products.

Evaluation of Sensititre Broth Microdilution Plate for determining the susceptibility of carbapenem-resistant Klebsiella pneumoniae to polymyxins.

Colistin and polymyxin B MICs were determined for 106 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates using Sensititre Research Use Only GNX2F plates (Thermo Fisher) and compared to CLSI broth macrodilution (BMD) as the reference method. For colistin, EUCAST breakpoints were applied and testing of isolates with very major (VM) errors was repeated in duplicate by both methods to determine a majority result. Essential agreement (MIC ± one dilution) of GNX2F with the reference method was 97.1% for polymyxin B and 92.5% for colistin (7 VM errors, 22.6%). After discrepancy testing, there were 28 colistin resistant isolates by BMD and essential agreement was 94.3% with 4 VM errors (14.3%). Colistin and polymyxin B GNX2F results showed acceptable essential agreement with BMD for MICS without interpretation. Colistin VM errors with EUCAST breakpoints were due to MIC variability in the 2 to 4 µg/mL range that could be addressed by establishing an intermediate category.

Monitoring of Biomedical License Agreements: A Practical Guide.

Because technology licensed from research organizations can play a significant role in drug innovation and the generation of novel biomedical products, licensee performance under such agreements must be effectively monitored. This is necessary so that resultant benefits, including public health improvement, may be returned to the innovator(s) as well as society at large. The tasks that comprise monitoring are varied, but all come under the general heading of 'enforcement of license provisions'.Since 1996, the license monitoring and enforcement program established by the US National Institutes of Health (NIH) Group has collected about $US17 million in unpaid and underpaid license royalties through formal financial audits and other investigative activities. During the same period, the Office of Technology Transfer (OTT) settled more than 60 cases of suspected patent infringement, generating around 60 new licenses and collected both back and ongoing royalties. As these numbers show, an active and effective monitoring program is an essential part of any technology transfer or biomedical licensing program.