Ruth Lynfield

Bio: Ruth Lynfield is an academic researcher from University of Rochester. The author has contributed to research in topics: Infectious disease (medical specialty) & Epidemiology. The author has an hindex of 15, co-authored 23 publications receiving 874 citations.

Trends in perinatal group B streptococcal disease - United States, 2000-2006.

Abstract: Group B Streptococcus (GBS) is a leading infectious cause of neonatal morbidity and mortality in the United States. The bacterium, a common colonizer of the maternal genital tract, can infect the fetus during gestation, causing fetal death. GBS also can be acquired by the fetus during passage through the birth canal or after delivery. Infection commonly manifests as meningitis, pneumonia, or sepsis. In 2002, CDC, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics issued revised guidelines for prevention of early-onset GBS disease (i.e., in infants aged <7 days). These guidelines recommended universal screening of all pregnant women for rectovaginal GBS colonization at 35-37 weeks' gestation and administration of intrapartum antibiotic prophylaxis (IAP) to carriers. A report published in 2007 indicated that, during 2003-2005, the overall rate of early-onset GBS disease increased, whereas incidence of late-onset GBS disease (i.e., in infants aged 7-89 days) remained stable. This report updates the 2007 report by incorporating 2006 data from the Active Bacterial Core surveillance (ABCs) system. The updated analysis revealed an increase in the overall rate of early-onset GBS disease from 2003 to 2006, driven by an increasing incidence among black term infants. Late-onset GBS disease incidence among black infants, which had increased during 2003-2005, declined in 2006. Continued monitoring is needed to follow trends in early-onset GBS disease among black infants to determine whether additional interventions are warranted.

Preliminary results: surveillance for Guillain-Barré Syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.

Abstract: Guillain-Barré syndrome (GBS) is an uncommon peripheral neuropathy causing paralysis and in severe cases respiratory failure and death. GBS often follows an antecedent gastrointestinal or upper respiratory illness but, in rare cases, can follow vaccination. In 1976, vaccination against a novel swine-origin influenza A (H1N1) virus was associated with a statistically significant increased risk for GBS in the 42 days after vaccination (approximately 10 excess cases per 1 million vaccinations), a consideration in halting the vaccination program in the context of limited influenza virus transmission. To monitor influenza A (H1N1) 2009 monovalent vaccine safety, several federal surveillance systems, including CDC's Emerging Infections Program (EIP), are being used. In October 2009, EIP began active surveillance to assess the risk for GBS after 2009 H1N1 vaccination. Preliminary results from an analysis in EIP comparing GBS patients hospitalized through March 31, 2010, who did and did not receive 2009 H1N1 vaccination showed an estimated age-adjusted rate ratio of 1.77 (GBS incidence of 1.92 per 100,000 person-years among vaccinated persons and 1.21 per 100,000 person-years among unvaccinated persons). If end-of-surveillance analysis confirms this finding, this would correspond to 0.8 excess cases of GBS per 1 million vaccinations, similar to that found in seasonal influenza vaccines. No other federal system to date has detected a statistically significant association between GBS and 2009 H1N1 vaccination. Surveillance and further analyses are ongoing. The 2009 H1N1 vaccine safety profile is similar to that for seasonal influenza vaccines, which have an excellent safety record. Vaccination remains the most effective method to prevent serious illness and death from 2009 H1N1 influenza infection; illness from the 2009 H1N1 influenza virus has been associated with a hospitalization rate of 222 per 1 million and a death rate of 9.7 per 1 million population.

Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae - United States, 2006-2007

Abstract: Streptococcus pneumoniae (pneumococcus) is a common cause of pneumonia and meningitis in the United States. Antimicrobial resistance, which can result in pneumococcal infection treatment failure, is identified by measuring the minimum inhibitory concentration (MIC) of an antimicrobial that will inhibit pneumococcal growth. Breakpoints are MICs that define infections as susceptible (treatable), intermediate (possibly treatable with higher doses), and resistant (not treatable) to certain antimicrobials. In January 2008, after a reevaluation that included more recent clinical studies, the Clinical and Laboratory Standards Institute (CLSI) published new S. pneumoniae breakpoints for penicillin (the preferred antimicrobial for susceptible S. pneumoniae infections). To assess the potential effects of the new breakpoints on susceptibility categorization, CDC applied them to MICs of invasive pneumococcal disease (IPD) isolates collected by the Active Bacterial Core surveillance (ABCs) system at sites in 10 states during 2006-2007. This report summarizes the results of that analysis, which found that the percentage of IPD nonmeningitis S. pneumoniae isolates categorized as susceptible, intermediate, and resistant to penicillin changed from 74.7%, 15.0%, and 10.3% under the former breakpoints to 93.2%, 5.6%, and 1.2%, respectively, under the new breakpoints. Microbiology laboratories should be aware of the new breakpoints to interpret pneumococcal susceptibility accurately, and clinicians should be aware of the breakpoints to prescribe antimicrobials appropriately for pneumococcal infections. State and local health departments also should be aware of the new breakpoints because they might result in a decrease in the number of reported cases of penicillin-resistant pneumococcus.

Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC.

Abstract: Despite substantial progress in prevention of perinatal group B streptococcal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States In 1996, CDC, in collaboration with relevant professional societies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC Prevention of perinatal group B streptococcal disease: a public health perspective MMWR 1996;45[No RR-7]); those guidelines were updated and republished in 2002 (CDC Prevention of perinatal group B streptococcal disease: revised guidelines from CDC MMWR 2002;51[No RR-11]) In June 2009, a meeting of clinical and public health representatives was held to reevaluate prevention strategies on the basis of data collected after the issuance of the 2002 guidelines This report presents CDC's updated guidelines, which have been endorsed by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the American College of Nurse-Midwives, the American Academy of Family Physicians, and the American Society for Microbiology The recommendations were made on the basis of available evidence when such evidence was sufficient and on expert opinion when available evidence was insufficient The key changes in the 2010 guidelines include the following: • expanded recommendations on laboratory methods for the identification of GBS, • clarification of the colony-count threshold required for reporting GBS detected in the urine of pregnant women, • updated algorithms for GBS screening and intrapartum chemoprophylaxis for women with preterm labor or preterm premature rupture of membranes, • a change in the recommended dose of penicillin-G for chemoprophylaxis, • updated prophylaxis regimens for women with penicillin allergy, and • a revised algorithm for management of newborns with respect to risk for early-onset GBS disease Universal screening at 35-37 weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns Although early-onset GBS disease has become relatively uncommon in recent years, the rates of maternal GBS colonization (and therefore the risk for early-onset GBS disease in the absence of intrapartum antibiotic prophylaxis) remain unchanged since the 1970s Continued efforts are needed to sustain and improve on the progress achieved in the prevention of GBS disease There also is a need to monitor for potential adverse consequences of intrapartum antibiotic prophylaxis (eg, emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens) In the absence of a licensed GBS vaccine, universal screening and intrapartum antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease prevention

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

Abstract: This report updates the 2009 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine---recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009. MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and updated information. Highlights of the 2010 recommendations include 1) a recommendation that annual vaccination be administered to all persons aged >or=6 months for the 2010-11 influenza season; 2) a recommendation that children aged 6 months--8 years whose vaccination status is unknown or who have never received seasonal influenza vaccine before (or who received seasonal vaccine for the first time in 2009-10 but received only 1 dose in their first year of vaccination) as well as children who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010--11 season; 3) a recommendation that vaccines containing the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5) information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications. Vaccination efforts should begin as soon as the 2010-11 seasonal influenza vaccine is available and continue through the influenza season. These recommendations also include a summary of safety data for U.S.-licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2010-11 influenza season also will be available at this website. Recommendations for influenza diagnosis and antiviral use will be published before the start of the 2010-11 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

Abstract: Background Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. Methods We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. Results A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). Conclusions Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Abstract: Importance: Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. Objective: To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. Design, Setting, and Participants: The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. Interventions: Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). Main Outcomes and Measures: The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). Results: Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49 for 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69) for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point. Trial Registration: ClinicalTrials.gov Identifier: NCT04427501.

Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis

Abstract: Summary: The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.