A pediatrician was listening to a news report on the radio discussing a government representative introducing legislation allowing emergency medical technicians to administer antibiotics to patients with suspected sepsis. The representative stated that this would allow sepsis patients to receive treatment earlier. While early antibiotic treatment is a great idea, the pediatrician began to think about several other potentially negative aspects of this policy such as decreased ability to identify the organisms due to antibiotic pretreatment, difficulty in making the diagnosis of sepsis initially and therefore patients would receive antibiotics that should not, increased antibiotic resistance, potential delay of transport to the hospital as the antibiotic is being given, decreased uptake of the antibiotic as it may need to be delivered by intramuscular than intravenous pathway, risk of allergic reactions, etc. He thought, “I wonder how much of a decrease there is in identifying the organism because of antibiotic pre-treatment?”
Sepsis is an inflammatory response syndrome in the presence of an infection, it can be caused by bacteria, viruses or fungi. Bacteremia is the presence of bacteria in the blood. Studies from the US show an increased incidence of sepsis (0.56 to 0.89 cases/1000 children in all age groups) but a decreased fatality rate from 10.3% to 8.9%. The prevalence of severe sepsis in pediatric intensive care settings is reported in as many as 7.7% of admissions. Severe sepsis is more common when patients have co-morbities. Primary prevention includes immunization and appropriate precautions and procedures (i.e. catheter access) in hospitalized children or those with chronic medical needs. Prophylactic antibiotics for patients with neutropenia are also a secondary intervention.
Sepsis can be difficult to diagnose in any patient and particularly in children; symptoms can be non-specific or vague. One of the biggest problems with sepsis treatment is its recognition. Body temperature may be inappropriately low or high, inappropriate tachycardia or mental status changes and reduced peripheral perfusion are clinical features of sepsis. Hypotension may not occur initially but it can also be difficult to obtain a blood pressure on a child. Mainstays of treatment are early antibiotic administration and supportive measures especially fluid resuscitation. Vasopressor medications also can help support patients. Obtaining peripheral and central access can be difficult in pediatric patients and can hinder resuscitation and treatment of sepsis.
Recovery of bacterial organisms from the human body depends on many factors including the specific organism, antibiotic pretreatment, specimen adequacy especially blood volume, specimen site and detection methods.
If patients are given antibiotics, there are blood culture systems designed to bind the antibiotics and allow the bacteria to grow for identification. A 2007 study found a decrease in recovery of various bacteria with antibiotics relative to control bottles with no antibiotics, showing that the binder systems are not complete. The percentage of bacteria recovered depended on the specific organisms, the specific antibiotic and the blood culture system. Of note for pediatric patients, no system recovered Streptococcus pneumoniae in the presence of ceftriaxone which is one of the most common bacteria causing bacteremia, sepsis or invasive disease in this age group and very often ceftriaxone is the first choice of antibiotics.
In a 2017 multi-institutional, international study of bacteria detection in children with pneumonia, “Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture.” There were also reductions in bacteria identification from other body sites and by different detection methods including polymerase chain reaction. They also found that “For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% …. from 2% when volume was ≤ 1 mL to approximately 6% for ≥ 3 mL.
In a 2016 study of blood culture yield relative to fever timing in children, they found that antibiotics before blood culture decreased the rate of positive blood cultures by almost 50% from 26.3% for no antibiotics to 12.7% with antibiotics (P <0.001). Additionally, they did not find a relationship to fever timing and blood sampling, noting "…timing of pediatric blood cultures relative to fever is unimportant. Bacteremia precedes a fever, but this is of limited clinical applicability."
A 2014, multi-center, U.S.-based study of timing of fever to blood culture positivity in young infants < 90 days old, found that the mean time from fever to blood culture positivity was 15.4 hours, and by 24, 36 and 48 hours, the blood culture had turned positive in 91%, 96% and 99% of babies. Only 6 babies had been pre-treated with antibiotics in this study, so pretreatment effects on blood culture results could not be assessed.
Questions for Further Discussion
1. What do you think about the potential public health policy of allowing emergency medical technicians to give antibiotics earlier? If so under what circumstances?
2. What antibiotics would be your first line treatment for neonates, young children or older children?
3. what are indications for placement of an intraosseous intravenous catheter or central line catheter?
- Symptom/Presentation: Hypotension and Shock
- Specialty: Critical Care | Emergency Medicine |
Pharmacology / Toxicology | Preventive Medicine and Health Maintenance
- Age: Not appropriate
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Flayhart D, Borek AP, Wakefield T, Dick J, Carroll KC. Comparison of BACTEC PLUS blood culture media to BacT/Alert FA blood culture media for detection of bacterial pathogens in samples containing therapeutic levels of antibiotics. J Clin Microbiol. 2007 Mar;45(3):816-21.
Riedel S, Bourbeau P, Swartz B, Brecher S, Carroll KC, Stamper PD, Dunne WM, McCardle T, Walk N, Fiebelkorn K, Sewell D, Richter SS, Beekmann S, Doern GV. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol. 2008 Apr;46(4):1381-5.
Kee PP, Chinnappan M, Nair A, Yeak D, Chen A, Starr M, Daley AJ, Cheng AC, Burgner D. Diagnostic Yield of Timing Blood Culture Collection Relative to Fever. Pediatr Infect Dis J. 2016 Aug;35(8):846-50.
Biondi EA, Mischler M, Jerardi KE, Statile AM, French J, Evans R, Lee V, Chen C, Asche C, Ren J, Shah SS; Pediatric Research in Inpatient Settings (PRIS) Network.
Blood culture time to positivity in febrile infants with bacteremia. JAMA Pediatr. 2014 Sep;168(9):844-9.
Plunkett A, Tong J. Sepsis in children. BMJ. 2015 Jun 9;350:h3017.
Melendez E, Bachur R. Quality improvement in pediatric sepsis. Curr Opin Pediatr. 2015 Jun;27(3):298-302.
Driscoll AJ, Deloria Knoll M, Hammitt LL, Baggett HC, Brooks WA, Feikin DR, et.al. The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia. Clin Infect Dis. 2017 Jun 15;64(suppl_3):S368-S377.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa