- Serious Bacterial Infections in Neonates: Is a Single Fever Enough?
- Short-Course Primaquine Non-Inferior to Standard Treatment for vivax Malaria
Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.
Reviewed by Terri Stillwell, MD
Evaluation for sepsis in febrile neonates is a common practice in emergency departments (EDs). Oftentimes, neonates present with a history of fever but are afebrile at presentation to the ED, leading clinicians to question whether a full sepsis evaluation is necessary. In a recent single-center, retrospective study in Pediatrics, the authors assessed whether presence, or lack, of ongoing fever impacted rates of serious bacterial infections (SBIs) and invasive bacterial infections (IBIs).
The study authors separated a cohort of febrile neonates (less than or equal to 28 days of age) into three categories: those who were febrile at presentation to the ED (FP); those with history of fever, afebrile at presentation to the ED, but who subsequently developed fever during admission (ASF); and those with history of fever, afebrile at presentation to the ED, who remained afebrile throughout admission (ANF). Each cohort was analyzed for rates of SBI (including urinary tract infection, bacteremia, and bacterial meningitis) and IBI (including bacteremia and bacterial meningitis).
Over more than a decade-long study period, 560 neonates were found to be febrile at presentation (60.2 percent), while 371 (39.8 percent) had history of fever but were afebrile at presentation, of which 93 (25.1 percent) were ASF and 278 were ANF (74.9 percent). Rates of SBI in neonates ANF (4.7 percent) were lower than neonates FP (10.4 percent), whereas rates of SBI were higher in neonates ASF (18.3 percent). Odds of IBI were comparable across all three groups. Neonates ANF had a median time to positive culture of 20.2 hours.
While children who solely presented with historical fever had less SBI, children with any report of fever remained at risk for SBI and IBI and should, therefore, receive a full sepsis evaluation. Those with historical fever without subsequent fever may be eligible for early discharge.
Reviewed by Daniel Mendoza, MD, PhD
The standard treatment to prevent P. vivax relapse is primaquine for 14 days, but adherence is frequently poor. In a randomized placebo-controlled clinical trial conducted in Africa and Asia, and recently described in Lancet, patients with normal glucose-6-phosphate dehydrogenase (G6PD) who presented with uncomplicated P. vivax malaria were enrolled. Patients were randomized to primaquine 1 mg/kg/day for 7 days, primaquine 0.5 mg/kg/day for 14 days, or placebo. The primary outcome was the incidence of symptomatic P. vivax parasitemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0.07 recurrences per person-year was used to establish non-inferiority.
The incidence of recurrent P. vivax malaria was 0.18 (95 percent confidence interval [CI] 0.15-0.21) recurrences per person-year for 935 patients in the 7-day primaquine group, 0.16 (CI 0.13-0.18) for 937 patients in the 14-day primaquine group, and 0.96 (CI 0.83-1.08) for 464 patients in the placebo group. The difference between the 7-day and 14-day primaquine groups was 0.02 (CI -0.02 to 0.05, P = 0.34). Approximately one third of patients did not complete the 12-month follow-up, mainly because of the late start of the study in Ethiopia. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in 9/935 (1 percent) patients in the 7-day group, 1/937 (0.1 percent) in the 14-day group, and 0/464 in the placebo group. The most common adverse events were gastrointestinal symptoms.
In patients with normal G6PD, 7-day treatment with primaquine was non-inferior to the standard 14-day treatment and had an acceptable safety and tolerability profile. These results suggest that the short-course regimen might improve adherence in endemic countries with malaria.