Impact of SARS-CoV-2 Resistance to Antiviral Monoclonal Antibody Therapy on Neutralizing Antibody Response.

Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations.

Rapid determination of SARS-CoV-2 antibody neutralization titer using Bio-Rad Bio-Plex correlates strongly with pseudovirus-determined neutralization titer.

Accurate and rapid evaluation of SARS-CoV-2 half-maximal neutralizing antibody (nAb) titer (NT50) is an important research tool for measuring nAb responses after prophylaxis or therapeutics for COVID-19 prevention and management. Compared with ACE2-competitive enzyme immunoassays for nAb detection, pseudovirus assays remain low-throughput and labor intensive. A novel application of the Bio-Rad Bio-Plex Pro Human SARS-CoV-2 D614G S1 Variant nAb Assay was used to determine NT50 from COVID-19-vaccinated individuals and showed strong correlation to a laboratory-developed SARS-CoV-2 pseudovirus nAb assay.

HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.

Introduction: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV.

Methods: MTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015.

Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa.

Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting formulation; however, increasing transmission of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to rilpivirine could reduce its preventive efficacy. This study investigated rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100 individuals failing on first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy in South Africa whose samples were sent for routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA > 10,000 copies/ml and ≥1 non-nucleoside reverse transcriptase inhibitor-resistance mutation in reverse transcriptase.

Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa.

A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation.

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma.

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.

Telephone assessment of functioning and well-being following stroke: is it feasible?

Stroke can affect the physical, emotional, and social aspects of patients' lives. The purpose of this study was to assess the feasibility and psychometric properties of a telephone-administered version of the Health Utilities Index Mark 2 and 3 (HUI2/3). Subjects included patients who had had an ischemic stroke within the prior 12 months and their unpaid caregivers (n = 76 pairs) and an additional 33 unpaid caregivers of patients who were generally aphasic or severely affected.

Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States.

Grepafloxacin potency and spectrum of activity were re-evaluated against contemporary pathogens collected from clinical infections in 2001-2002. A total of 995 isolates were tested for grepafloxacin by the reference agar dilution method and these results were compared to those of 25 other antimicrobial agents. Grepafloxacin activity remained comparable to that of ciprofloxacin, levofloxacin and gatifloxacin against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (MIC(90), 0.

Comparison of Streptococcus pneumoniae and Haemophilus influenzae susceptibilities from community-acquired respiratory tract infections and hospitalized patients with pneumonia: five-year results for the SENTRY Antimicrobial Surveillance Program.

The SENTRY Antimicrobial Surveillance Program has been monitoring the activity of commonly prescribed and novel antimicrobial agents on a global scale from 1997 to the present. Specific objectives have documented the key resistance rates among pathogens from both patients hospitalized with pneumonia and those diagnosed with community-acquired pneumonia. Hemophilus influenzae and Streptococcus pneumoniae are common pathogens in both of these patient populations and the susceptibility profiles for these two species were compared to distinguish potential differences that may be evident in North American surveillance (1997-2001).

Commercial broth microdilution panel validation and reproducibility trials for garenoxacin (BMS-284756), a novel desfluoroquinolone.

Results from garenoxacin dry-form broth microdilution MIC panels prepared commercially (Sensititre, TREK Diagnostics) were compared to reference frozen-form MICs to ensure the validity of the longer-shelf-life product. A total of 1078 organisms from seven major organism groups were used in this trial. All commercial MIC results were within +/- one log(2) dilution of reference garenoxacin values, and reproducibility trials produced identical MIC results for 90.

Susceptibility patterns of orally administered antimicrobials among urinary tract infection pathogens from hospitalized patients in North America: comparison report to Europe and Latin America. Results from the SENTRY Antimicrobial Surveillance Program (2000).

Urinary tract infections (UTIs) remain a worldwide nosocomial infection problem. Geographic variations in pathogen occurrence and susceptibility profiles require monitoring to provide information to guide new (garenoxacin [BMS284756]) therapeutic options. Two thousand seven hundred-eighty UTI isolates from Europe (n = 783), Latin America (531), and North America (1,466) were tested and compared against 44 agents by reference methods in the SENTRY Antimicrobial Surveillance Program.

Antimicrobial susceptibility patterns of beta-hemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997-2000).

Susceptibility patterns of 15 antimicrobial agents were assessed for 3,400 isolates of beta-hemolytic (betahS) and viridans group (VgS) streptococci in the four regions of the SENTRY Antimicrobial Surveillance Program: Asia-Pacific (APAC), Europe (EU), Latin America (LA) and North America (NA). In 1997 through 2000, SENTRY Program monitors tested strains by reference broth microdilution methods and results were interpreted using National Committee for Clinical Laboratory Standards criteria. Among the betahS processed, 81.

BMS284756 (formerly T-3811, a des-fluoroquinolone) potency and spectrum tested against over 10,000 bacterial bloodstream infection isolates from the SENTRY antimicrobial surveillance programme (2000).

BMS284756 is a novel des-F (6)-quinolone, which has a wide range of activity against many species of Gram-positive and -negative organisms. The potency of BMS284756 was compared with that of other quinolones, including ciprofloxacin, gatifloxacin and levofloxacin, and was tested against >10,000 bloodstream isolates from the year 2000 SENTRY antimicrobial surveillance programme. Twelve pathogens accounted for nearly all of the referred isolates and included Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp.