What’s New in ID? December 2019 / Prosinac 2019.

Clinical phenotypes in sepsis

Clinical phenotypes have been proposed as a potential way to identify those most at risk of dying from sepsis. In a retrospective analysis of sepsis datasets that comprised over 20,000 patients, four phenotypes were identified. An alpha phenotype (patients on lowest dose of a vasopressor) had the lowest mortality (5 percent) while the beta phenotype (older patients with chronic illnesses and renal dysfunction) had a mortality of 13 percent, the gamma phenotype (patients with inflammation and pulmonary dysfunction) had a mortality of 24 percent, and the delta phenotype (patients with liver dysfunction and septic shock) had the highest mortality at 40 percent. While these data are helpful in understanding the clinical heterogeneity of sepsis, further studies are needed to determine their utility in clinical practice.

Seymour CW, Kennedy JN, Wang S, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA 2019; 321:2003

New pneumococcal vaccination recommendations for adults ≥65 years old

The United States Advisory Committee on Immunization Practices has updated its pneumococcal vaccination recommendations for adults ≥65 years old. The committee continues to recommend routine vaccination with the 23-valent pneumococcal vaccine (PPSV23) for all adults in this age group. Shared decision making is now recommended to determine whether the 13-valent pneumococcal conjugate vaccine (PCV13) should be given in addition to PPSV23 for adults ≥65 years old who otherwise lack an indication for both vaccines (eg, an immunocompromising condition). The change from the prior recommendations to give both vaccines to all persons in this age group is based on the dramatic decline in the incidence of PCV13-type infections resulting from universal PCV13 vaccination in childhood. We concur with this new recommendation. For most otherwise healthy adults ≥65 years old, we consider the absolute risk of acquiring pneumococcal disease caused by a PCV13 serotype to be low, and the expected benefit of the additional vaccination is very small.

Matanock A, Lee G, Gierke R, et al. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2019; 68:1069.

Prednisolone for mild croup

Glucocorticoid therapy is a standard part of croup management, and dexamethasone is the agent most commonly used in the emergency department and inpatient settings. Whether prednisolone, more widely available in outpatient settings, is equally effective is uncertain, and earlier trials have reported higher rates of return visits for children treated with prednisolone. In a recent randomized trial involving >1200 children with mild croup, symptom improvement was similar in patients treated with a single dose of oral prednisolone or dexamethasone and an increased risk of symptom recurrence with prednisolone was not detected. Based on these findings, either agent is acceptable for the treatment of mild croup.

Parker CM, Cooper MN. Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Pediatrics 2019; 144.

CSF analysis in well-appearing young febrile infants with UTIs

The need to perform a lumbar puncture to obtain cerebrospinal fluid (CSF) for analysis in otherwise low-risk, well-appearing febrile infants with urinary tract infections (UTIs) has been questioned. In a systematic review and meta-analysis of nearly 3900 infants 29 to 90 days of age (20 observational studies), the pooled prevalence of bacterial meningitis in those infants with UTIs was 0.25 percent. Sterile CSF pleocytosis was variably reported (in up to 29 percent of patients with UTIs), leading to unnecessary additional antibiotic coverage for suspected meningitis pending culture results. These findings support avoiding lumbar puncture in otherwise low-risk, well-appearing febrile young infants 29 to 90 days of age with UTIs.

Nugent J, Childers M, Singh-Miller N, et al. Risk of Meningitis in Infants Aged 29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-Analysis. J Pediatr 2019; 212:102.

Rotavirus vaccine and intussusception

Post-licensure surveillance suggested a very small increased risk of intussusception within 21 days of receipt of currently licensed rotavirus vaccines (approximately 1 in 20,000 to 1 in 100,000 vaccine recipients). Although randomized trials may not detect rare adverse effects, in two recent meta-analyses of placebo-controlled randomized trials (each including >200,000 participants), rates of intussusception were similar in the rotavirus vaccine and placebo groups. These findings provide reassurance that the risk of intussusception after rotavirus vaccination is much lower than the risk of severe rotavirus gastroenteritis in unvaccinated children and support recommendations for universal rotavirus vaccination.

Soares-Weiser K, Bergman H, Henschke N, et al. Vaccines for preventing rotavirus diarrhea: vaccines in use. Cochrane Database Syst Rev 2019; 3:CD008521.

Lu HL, Ding Y, Goyal H, Xu HG. Association Between Rotavirus Vaccination and Risk of Intussusception Among Neonates and Infants: A Systematic Review and Meta-analysis. JAMA Netw Open 2019; 2:e1912458.

Indeterminate HIV nucleic acid test results in infants

Prompt and accurate diagnosis of HIV infection in HIV-exposed infants is critical. However, as access to HIV testing for exposed infants has expanded, concerns have emerged regarding the treatment implications of indeterminate and false-positive nucleic acid test (NAT) results. In a systematic review and meta-analysis of 32 studies (>1.3 million infants), indeterminate (or “weakly positive”) results accounted for 17 percent of over 14,700 initial non-negative NAT results; three-quarters of the indeterminate results were negative on repeat testing. These findings highlight the importance of serial testing to establish or exclude the diagnosis of HIV infection in infants born to HIV-infected mothers.

Luo R, Boeras D, Broyles LN, et al. Use of an Indeterminate Range in HIV Early Infant Diagnosis: A Systematic Review and Meta-Analysis. J Acquir Immune Defic Syndr 2019; 82:281.

No role for antiretroviral monotherapy

Patients with HIV and a suppressed viral load who need to switch their antiretroviral therapy (ART) regimen can safely transition to certain two-drug regimens. However, single-drug regimens should not be used, even if the agent has a high barrier to resistance. In a study of patients with a suppressed viral load on dolutegravir-abacavir-lamivudine, almost 10 percent of those who switched to dolutegravir alone had a virologic breakthrough, and two patients developed resistance to integrase inhibitors; by contrast, the patients who stayed on their initial regimen remained suppressed. Combination ART remains the only viable treatment strategy for persons with HIV.

Hocqueloux L, Raffi F, Prazuck T, et al. Dolutegravir Monotherapy Versus Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed People Living With Chronic Human Immunodeficiency Virus Infection: The Randomized Noninferiority MONotherapy of TiviCAY Trial. Clin Infect Dis 2019; 69:1498.

Outcomes for Zika virus-exposed infants in the second year of life

The prognosis of infants born to mothers with Zika virus infection during pregnancy is uncertain, and long-term data are lacking. In an observational study from Brazil of 216 infants with in utero Zika virus exposure who were prospectively followed for the first two years of life, findings noted in the newborn period were often not predictive of later outcomes. Approximately one-half of infants who had abnormal neurologic examination or neuroimaging findings at birth went on to have normal development on follow-up assessments. In addition, approximately one-quarter of infants without symptoms at birth went on to have developmental delays and/or abnormal hearing or vision at follow-up. These findings underscore the need for long-term follow-up of all children with confirmed or suspected in utero Zika virus exposure.

Nielsen-Saines K, Brasil P, Kerin T, et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat Med 2019; 25:1213.

Modified vaccinia Ankara vaccine for prevention of smallpox

In the United States, a replication-competent smallpox vaccine (ACAM2000) has been available when smallpox vaccination is indicated for select individuals (eg, some laboratory researchers and military personnel) and for stockpile in case of a public health emergency. In September 2019, the US Food and Drug Administration approved a replication-deficient modified vaccinia Ankara vaccine (MVA), which has been available in other countries, for the prevention of smallpox and monkeypox. Clinical trials have found that this vaccine is safe and immunogenic; its potential efficacy against smallpox was suggested by a study in which it reduced the rate of major cutaneous reactions induced by ACAM2000. Unlike replication-competent vaccines, MVA can be administered to immunocompromised patients and those with skin disorders. However, the precise role of this vaccine in smallpox prevention is yet to be determined.

US Food and Drug Administration. FDA approves first live, the non-replicating vaccine to prevent smallpox and monkeypox. https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and-monkeypox (Accessed on October 23, 2019).

Pittman PR, Hahn M, Lee HS, et al. Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox. N Engl J Med 2019; 381:1897.

Source: Uptodate, December, 2019.