Anti-infective treatment of sepsis in children, do you know these problems?

Medical Pulse Is Compiled and Collated, please do not reprint without authorization.

Sepsis is a fatal response to infection and has become a major public health problem worldwide. Sepsis and septic shock in children are pathogenic syndromes caused by serious infections that require prompt detection and treatment, with studies showing a global case fatality rate of 25% for sepsis in children and as high as 36.6% in Asia. Reversing the shock state and treating potential infections causing sepsis are the main treatment targets, and anti-infective treatment of children with sepsis faces significant challenges, given the high rate of infection with resistant bacteria in children and the limited variety of anti-infective drugs available.

1

Empiric antibacterial therapy

Prior to obtaining microbial culture results, the selection of empiric antimicrobials that are active against possible pathogens is critical to obtaining the best therapeutic outcomes. The choice of agent in empiric anti-infective therapy depends primarily on the epidemiological characteristics of the pathogen at the site of infection and the status of antimicrobial resistance. The 2020 Rescue Sepsis Campaign (SCC) Guidelines for the Administration of Sepsis in Children recommend the early use of antibiotics (within 1 hour in patients with septic shock and within 3 hours in patients with sepsis-related organ disorders) and the initial empiric use of broad-spectrum antibiotics.

Table 1 Alternative antibiotics for sepsis in children

Common infections that cause sepsis include respiratory tract infections, bacteremia, intra-abdominal infections, central nervous system infections, genitourinary infections, and skin infections. In children with sepsis, gram-positive and gram-negative bacteria are responsible for many infections and should be considered the main target of antimicrobial coverage. In general, patients with septic shock due to viral diseases have a better prognosis than those with bacterial infection. Fungal infections are a rare cause of sepsis in children, may occur in immunocompromised and premature infants, and empiric antifungal therapy is generally not indicated.

2

Timing of antibacterial treatment

Timely and appropriate antimicrobial therapy for children with sepsis is important. However, due to different bacteriological and host factors, the optimal timing of the drug is still controversial. In patients with septic shock, SSC guidelines encourage the conduct of reasonable blood cultures, starting antibacterial therapy within 1 hour after confirming the results.

3

Dosage selection of antibacterial drugs

The choice of antibacterial drug dosage for sepsis in children balances efficacy and safety. Insufficient dose not only can not control the infection, but may induce drug resistance; too high a dose will increase the risk of medication and even induce drug-borne diseases. The current increasing incidence of multidrug-resistant infections worldwide, combined with the specific pathophysiology of children with sepsis, poses greater challenges in determining the appropriate dose of medication for children with sepsis.

Taking into account the increase in the volume of distribution in sepsis, even in the presence of organ dysfunction, the dosage should not be reduced for the first time with antibacterial drugs. Usually in the treatment of sepsis use the maximum dose recommended in the drug label to achieve the therapeutic concentration. Therapeutic drug monitoring may be considered clinically, but it is important to note that due to rapid changes in pharmacokinetics in the first 24 to 48 hours of sepsis, early drug levels are unlikely to determine long-term dosing needs. With changes in organ function and fluid status, the dose of application of antibacterial drugs should be re-evaluated daily. Since most antimicrobials are metabolized through the kidneys, renal function should be a primary consideration when adjusting the dose.

4

Combination of drugs

Combination of drugs includes the combination of different types of drugs and different routes of administration for the same pathogen, such as the combination of two or three drugs in the case of drug-resistant bacteria infection, exerting antibacterial effects through different mechanisms of action of drugs, and improving the cure rate of the disease; intravenous infusion combined with intrathecal injection therapy in meningitis, etc., which can increase the drug concentration at the site of infection. In addition, in empiric antimicrobial therapy, a combination of drugs with different antimicrobial spectrums can be applied according to the possible pathogen to cover different pathogens. However, SCC guidelines do not recommend combinations in children with non-immunocompromised and/or low risk of multidrug resistance.

5

Course of antibacterial therapy and medication reduction

The duration of antimicrobial therapy for sepsis in children should be determined according to the site of infection, microbial etiology, pathogen burden, positive culture time, and clinical features. During treatment of sepsis, a comprehensive assessment of efficacy should be conducted in conjunction with clinical, imaging, and laboratory results to minimize the duration of antibiotic therapy. For some diseases that require long-term treatment, sequential treatment with oral drugs with good bioavailability may be selected. SCC guidelines recommend optimizing antimicrobial dosing strategies based on pharmacokinetics/pharmacodynamics and drug properties, and recommend daily antibiotic downgrade assessments.

Resources:

1.Burgunder L, Heyrend C. et al. Medication and Fluid Management of Pediatric Sepsis and Septic Shock. Paediatr Drugs. 2022 Mar 21. doi: 10.1007/s40272-022-00497-z. Epub ahead of print. PMID: 35307800.

2.Weiss SL, Peters MJ,et al. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020 Feb;21(2):e52-e106. doi: 10.1097/PCC.0000000000002198. PMID: 32032273.

3. YangMei, Qian Suyun. Optimized anti-infective therapy for sepsis in children: Details determine success or failure[J]. Chinese Journal of Emergency Medicine,2019,28(6):666-669.