Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England
Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England
The United Kingdom introduced a meningococcal group B vaccine (4CMenB, Bexero) into the national immunization program from September 2015, with two-dose schedule for infants and a 12-month booster. The effects of vaccination were evaluated against the incidence of meningococcal group B disease. During the first year since vaccine introduction, there was a 75% reduction of meningococcal group B disease incidence in age groups fully eligible for vaccination. The 4CMenB program positively affected meningococcal group B disease incidence in children in the UK, with sustained protection for at least 2 years following three doses of the vaccine.
Ladhani SN, Andrews N, Parikh SR, Campbell H, White J, Edelstein M et al. Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England. N Engl J Med 2020; 382:309-317.
Increased risk of active tuberculosis during pregnancy and postpartum
There are no clear conclusions on the risk o active tuberculosis in pregnancy. This study retrospectively analyzed data from childbirth and tuberculosis registers regarding women aged 15-49 who gave birth in Sweden between 2005 and 2013. The study showed an increased risk of active tuberculosis in pregnancy and the postpartum period in women from high incidence countries (with tuberculosis incidence 100 or higher per 100 000 person-years). Therefore, tuberculosis screening is recommended in pregnant women from high incidence countries.
Jonsson J, Kühlmann-Berenzon S, Berggren I, Bruchfeld J. Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden. Eur Respir J. 2019 Dec 20. pii: 1901886.
Balanced Crystalloids versus Saline in Sepsis
Despite intravenous crystalloid solution administration being an agreed part of sepsis treatment, there is no consensus on crystalloid composition benefits. This study did a secondary analysis of patients from Isotonic Solutions and Major Adverse Renal Events Trial (SMART) and compared the effects of balanced crystalloids and saline on 30-day hospital mortality among ICU patients admitted for sepsis. Patients who received balanced solutions had less major adverse kidney events, less renal replacement therapy days and less vasopressor therapy days. Balanced crystalloids were also associated with lower hospital mortality within 30 days in comparison to saline.
Brown RM, Wang L, Coston TD, Krishnan NI, Casey JD, Wanderer JP et al. Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 15;200(12):1487-1495
Long-term outcome of patients with non-operated prosthetic valve infective endocarditis
Indications for surgery are similar for prosthetic and native valve endocarditis; however long term outcome in prosthetic valve endocarditis following medical treatment alone is largely unknown. This study analyzed 129 non-operated patients with endocarditis of prosthetic valve alive at discharge at 6 weeks. Mortality at one year was 24%, relapses and reinfection were only 5% each, with Enterococcal endocarditis having the highest risk of relapse and no relapses in patients with cardiac abscesses.
Lecomte R, Laine JB, Issa N, Revest M, Gaborit B, Le Turnier P et al. Long-term outcome of patients with non-operated prosthetic valve infective endocarditis: is relapse the main issue? Clin Infect Dis. 2019 Dec 9. pii: ciz1177.
Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection
Previous manufacturer-funded study (MODIFY I) concluded that Bezlotoxumab, Clostridioides difficile toxin B human monoclonal antibody, when added to standard-of-care therapy has led to comparable clinical cure rates, but lower 12-week recurrence rate. This study (MODIFY II) was conducted to assess long-term outcomes following Bezlotoxumab therapy. No patients with sustained clinical cure at 12 weeks following treatment-experienced recurrent episodes of Clostritioides difficile infection after 9 months. Bezlotoxumab has been approved for adult use by FDA and appears to prevent Clostrodioides difficile recurrence, but its cost renders it inaccessible in many healthcare systems for now.
Goldstein EJC, Citron DM, Gerding DN, Wilcox MH, Gabryelski L, Pedley A, et al. Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection: 12-Month Observational Data From the Randomized Phase III Trial, MODIFY II. Clin Infect Dis. 2019 Dec 23. pii: ciz1151.
Asthma and the Risk of Invasive Pneumococcal Disease
Invasive pneumococcal disease and pneumonia are common causes of morbidity and mortality in all ages, and asthma is the most common chronic disease of childhood. This meta-analysis reviewed five cohort studies from different countries in order to evaluate the risk of invasive pneumococcal disease or pneumonia in children with asthma following pneumococcal conjugate vaccines introduction, excluding children who received 23-valent pneumococcal polysaccharide vaccination. The conclusion was that children with asthma, despite pneumococcal conjugate vaccines, had 90% higher odds of invasive pneumococcal disease compared to healthy controls.
Castro-Rodriguez JA, Abarca K and Forno E. Asthma and the Risk of Invasive Pneumococcal Disease: A Meta-analysis. Pediatrics. 2020 Jan;145(1). pii: e20191200.
Antibacterial prophylaxis for patients with multiple myeloma
Multiple myeloma (MM) is associated with marked immunodeficiency and recurrent severe infections, especially during the first three months following diagnosis. In a multicenter randomized trial of over 950 adults with newly diagnosed MM, rates of febrile episodes (18 versus 23 percent) and mortality (0.8 versus 3 percent) were decreased with levofloxacin prophylaxis given for 12 weeks at the start of therapy compared with placebo. Serious adverse event rates were similar between groups apart from a higher rate of reversible tendinopathies (1 percent) with levofloxacin use. The acquisition of multidrug-resistant organisms and Clostridioides difficile did not differ between groups. This trial supports our practice to provide levofloxacin prophylaxis to patients with newly diagnosed MM during the first three months of treatment.
Drayson MT, Bowcock S, Planche T, Iqbal G, Pratt G, Yong K, Wood J, Raynes K, Higgins H, Dawkins B, Meads D, Hulme CT, Monahan I, Karunanithi K, Dignum H, Belsham E, Neilson J, Harrison B, Lokare A, Campbell G, Hamblin M, Hawkey P, Whittaker AC, Low E, Dunn JA; TEAMM Trial Management Group and Trial Investigators. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomized, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1760-1772.
No role for routine beta-lactam combination therapy for MRSA bacteremia
Standard treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia consists of monotherapy with vancomycin or daptomycin; in vitro and observational studies have suggested a potential benefit of adding a beta-lactam. However, in a randomized trial of more than 300 patients with MRSA bacteremia, the addition of an antistaphylococcal beta-lactam (flucloxacillin, cloxacillin, or cefazolin) to either vancomycin or daptomycin did not reduce the combined endpoint of mortality, persistent bacteremia, relapse, and treatment failure. Nephrotoxicity occurred more frequently in the combination therapy group, leading to early termination for safety. These data indicate that there is no role for routine use of combination therapy with a beta-lactam for the treatment of MRSA bacteremia.
Tong SYC, Lye DC, Yahav D, Sud A, Robinson JO, Nelson J, et al. Australasian Society for Infectious Diseases Clinical Research Network. Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Feb 11;323(6):527-537.
Measles susceptibility in infants younger than 12 months
Although the first dose of measles-containing vaccine (MCV) is usually administered at ≥12 months of age in countries where measles has been eliminated, most infants are susceptible to measles before 12 months because of waning maternal antibody protection. An observational study analyzed measles antibody titers from nearly 200 infants in Canada according to age. By three months of age, only 8 percent of infants had protective titers and, by six months of age, no infants did. These findings underscore the importance of measles prophylaxis (with MCV or immune globulin) for infants <12 months of age who are exposed to measles, as well as those who live in or travel to an area where there is a measles outbreak or where measles has not been eliminated.
Science M, Savage R, Severini A, McLachlan E, Hughes SL, Arnold C, Richardson S, Crowcroft N, Deeks S, Halperin S, Brown K, Hatchette T, Gubbay J, Mazzulli T, Bolotin S. Measles Antibody Levels in Young Infants. Pediatrics. 2019 Dec;144(6). pii: e20190630.
Source: Medline 2020.
At its February meeting, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended two antibacterial agents: cefiderocol and a generic version of tigecycline.
Cefiderocol (Fetcroja, Shionogi BV) is for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.
Cefiderocol is a siderophore cephalosporin that inhibits formation of peptidoglycan, a key component of the bacterial cell wall. It will be available as a 1-g powder for concentrate for solution for infusion.
Cefiderocol has been shown to “effectively” treat aerobic Gram-negative infections, the EMA said in summary statement. The most common side effects of cefiderocol are diarrhea, vomiting, nausea, and cough.
The CHMP also recommended marketing authorization for a generic version of tigecycline (Tigecycline Accord, Accord Healthcare) for adults and children as young as age 8 years with complicated skin and soft tissue infections (excluding diabetic foot infections) and complicated intra-abdominal infections.
Tigecycline Accord is a generic of Tygacil, which has been on the market in the European Union since 2006.
“Studies have demonstrated the satisfactory quality of Tigecycline Accord. Since Tigecycline Accord is administered intravenously and is 100% bioavailable, a bioequivalence study versus the reference product Tygacil was not required,” the EMA said in a summary statement.
The agency recommends that both cefiderocol and generic tigecycline be prescribed by physicians experienced in the management of infectious diseases.
Detailed recommendations for the use of these drugs will be included in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after marketing authorization has been granted by the European Commission.