Paediatrics



Antimicrobial treatment for children







Paediatric antimicrobial therapy can make the difference between cure and long-term disability and, in some cases, even death. Prescribing antimicrobial therapy to the paediatric patient is significantly different from treating the adult population. Thomas Omogi R.N. looks at the issue.

There are very few studies producing pharmacokinetic data for antimicrobial agents in children and adolescents. Paediatric patients require special nursing and intravenous infusion skills and may present an increased risk for complications. The most important considerations of paediatric antimicrobial therapy include:

• Obtaining an accurate diagnosis of infection

• Understanding the difference between empiric and definitive therapy

• Identifying opportunities to switch to narrow-spectrum antibiotics

• Selecting the most cost-effective oral agents to be given for the shortest amount of time

• Understanding the characteristics specific to antimicrobial agents

• Accounting for host characteristics that influence antimicrobial activity

• Recognizing potential adverse effects of antimicrobial agents on the paediatric patient

Antimicrobial therapy treats viral, bacterial and fungal infections. Invasive fungal infections have increased in frequency and severity in adult and paediatric populations in the past few decades.

Antimicrobial therapy is the primary treatment for presumed bacterial infection in the paediatric patient. Drug selection for paediatric patients is similar to that in adults because infecting organisms and their sensitivities are not age-specific. Several factors, however, affect dose and frequency. Age and weight are primary considerations when selecting drugs for antimicrobial therapy.

Lower Respiratory Tract Infections

Lower Respiratory Tract Infections (LRTI) cause disease in alveolar sacs resulting in pneumonia. The incidence and mortality rates for LRTI are higher in the United States than for any other infectious disease2. Nearly 30% of total deaths worldwide occur in children under the age of 5 years.

Bronchiolitis and pneumonia are the most common LRTIs in children3. LRTIs most frequently present coughs and increased respiratory rate. Lower chest wall indrawing may occur with more severe disease. Bronchiolitis and pneumonia present similar signs and symptoms, so differentiating the two may be problematic.

Bronchiolities primarily occurs in children less than one year old but appears less frequently in the second and third years of life. Signs include fever, rapid respirations, wheezing and lower chest wall indrawing. Viruses and respiratory syncytial virus (RSV) are the most common causes of LRTIs. Pneumonia may have viral or bacterial causes. Streptococcus pneumonia (pneumococcus) or Haemophilus influenza, especially type b (Hib) are common causes of bacterial pneumonia, which is rarely the result of infection by Staphylococcus aureus or other streptococci. Upper respiratory tract colonization and aspiration of contaminated excretions often leads to bacterial pneumonia in young children.

A 2013 study published in Paediatrics compared narrow and broad-spectrum antimicrobial therapies for paediatric patients hospitalized with pneumonia4. Researchers in that study performed a retrospective cohort study using information gathered from 43 children’s hospitals. The scientists wanted to compare outcomes and resource utilization among children hospitalized with community- acquired pneumonia (CAP) between 2005 and 2011 and who received either narrowspectrum antimicrobial therapy in the form of parenteral ampicillin/penicillin or broadspectrum ceftriaxone/cefotaxime.

In that study, 13,954 children received broad-spectrum therapy (89.7%) and 1,610 received narrow-spectrum therapy (10.3%). The median length of stay was three days in both groups. Nearly the same percentage of paediatric patients was admitted to intensive care and readmission rates were similar at 2.3% and 2.4% for those receiving broad-spectrum therapy and narrow-spectrum therapies respectively.

Median costs for hospitalization were nearly the same too, at US$3,992 for those undergoing broad-spectrum therapy and US$4,375 for those receiving narrowspectrum therapies.

The researchers concluded that there were no differences in clinical outcomes or costs for children hospitalized with CAP between treatment using narrow-spectrum therapy and those using broad-spectrum therapies.

Eye Infections

Eye infections in very young paediatric patients can present some special concerns. Selecting the best treatment depends on the type of eye infection. Distinguishing between the various types of eye infections can be challenging, however, because symptoms can be nonspecific or indeterminate.

Conjunctivitis is the most common eye infection to affect children5. There are several types of eye infections, including:

• Staphylococcal blepharitis – often caused by S aureus or Staphylococcus epidermidis

• Acute bacterial conjunctivitis – often caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis

• Neonatal bacterial conjunctivitis – often caused by Chlamydia trachomatis or Neisseria gonorrhoeae

• Viral conjunctivitis – adenovirus is the most common cause but may be caused by herpes simplex virus or varicella zoster virus

Skin and soft tissue infections

The incidence of skin and soft tissue infections has increased in the past decade, largely due to the emergence of community acquired methicillin-resistant Staphylococcus aureus (AC-MRSA).

One study shows that invasive MRSA infection in children disproportionately affects young infants. In that study of 876 paediatric cases of invasive MRSA, 39% were among infants6. Infants under the age of 90 days were at special risk when compared with older children, at 43.9 vs. 2.0 per 100,000. The researchers also noted that the incidence of invasive CA-MRSA is declining among adults but that it was rising in children; infection per 100,000 children increased from 1.1 in 2005 to 1.7 in 2010.

Selection of the appropriate antimicrobial therapy depends on determining the most likely causative organism. Practitioners should prescribe the most narrowspectrum antibiotic that still covers the likely organisms. Additionally, prescribers should consider the cost, product taste and dosing schedule to ensure compliance among paediatric patients and their parents. It is also essential to ensure the patient has no allergies or sensitivities to the prescribed class of antibiotics.

Central Nervous System infections

Central nervous system (CNS) infections are life threatening, especially to children. Many agents can cause infection within the central nervous system, often with involvement of the meninges, brain or spinal cord, or present as a space-occupying lesion. Diagnosis relies on epidemiological considerations, cerebrospinal fluid analysis, and appreciation of any presenting clinical syndromes, such as acute bacterial meningitis, acute aseptic meningitis, chronic meningitis or space-occupying lesions. Modern imaging techniques can help define the infected anatomic region, help evaluate treatment efficacy, and pinpoint causes outside of the central nervous system, such as mastoiditis or sinusitis.

The effect of an invasive fungal infection can be particularly devastating, especially among immunosuppressed neonates and children. Paediatric patients with primary and secondary immunodeficiencies are at special risk. The most commonly isolated organisms in the paediatric population are candida and Aspergillus. Timely diagnosis and initiation of appropriate antimicrobial therapy is essential for positive treatment outcomes.

Choosing among antifungal agents polyenes, azoles, and echinocandins

Proper antibiotic prescribing is an important medical practice, especially in paediatrics. Antibiotic therapy may be initiated as empiric therapy in the absence of a culture and sensitivity, specific therapy based on C&S, and prophylaxis to prevent illness.

There are several ways to classify antibiotics, including bacterial spectrum, type of activity, and chemical structure. Antibiotics within a class generally have similar patterns of effectiveness, toxicity and allergic potential.

There are three classes of antifungals currently available for treating systemic fungal infections – polyenes, azoles, and echinocandins. The newest agents offer potentially improved efficacy and less toxicity in difficult infections. Extended-spectrum azoles demonstrate excellent in vitro activity against Aspergillus and improve clinical outcomes. Echinocandins offer a broad spectrum of activity for Candida. Amphotericin is currently the treatment option of choice for zycomycosis, but posaconazole shows tremendous promise as a treatment option.

Polyene antifungal drugs

Polyene antifungal drugs, such as Amphotericin, nystatin and pimaricin, interact with sterols in the cell membrane. This interaction forms channels through which small molecules leak from the inside the fungal cell to the exterior of the cell.

Polyene antifungal drugs are not absorbed when taken orally, so these drugs effectively treat fungal infections affecting the gastrointestinal tract, including oral thrush. To treat systemic fungal infections, polyene must be administered intravenously.

Azole antifungal drugs

Azole antifungal drugs, such as fluconazole, ketoconazole, and itraconazole inhibit cytochrome P450-dependent enzymes. These enzymes, particularly C14 dementhylase, are involved in ergosterol biosynthesis that is critical to fungal cell membrane structure and its function. Azole drugs are broad-spectrum drugs that effectively treat fungal infections of the skin or mouth.

Echinocandins antifungal drugs

Echinocandins target the fungal cell wall. Echinocandins are lipopeptide molecules, which noncompetitively inhibit beta-dglucan synthase enzyme that forms glucan. Because glucan is a major component of fungal cell walls, inhibiting its synthesis damages the fungal cell wall.

Echinocandin injection treats systemic infection, especially those types of infections frequently affecting immunocompromised patients. Due to their large molecular size and poor bioavailability, echinocandins are available for intravenous administration. Safety and efficacy of many echinocandins, including caspofungin, micafungin, and anidulafungin, has not been established in paediatric patients10.

Antimicrobial therapy for newborns

Improved obstetrical management approaches and use of intrapartum antimicrobial therapy is reducing the incidence of early-onset neonatal sepsis but this condition remains one of the most common causes of neonatal morbidity and mortality in preterm babies. Identification of neonates at risk relies largely on perinatal risk factors that are not specific or sensitive.

The American Academy of Pediatrics says that broad-spectrum antimicrobial agents, such as ampicillin and an aminoglycoside, are the optimal treatment for infants with suspected early-onset sepsis11. Treatment should begin with diagnostic testing; the clinician should narrow the antimicrobial therapy upon identification of the pathogen. Prolonged empirical treatment (=5 days) with broad-spectrum antibiotics may increase the risk for late onset sepsis, necrotizing enterocolitis, and mortality. Discontinuation of antimicrobial therapy after 49 hours reduces these risks in clinical situations where the paediatric patient has a low probability of sepsis. Aminoglycosides, penicillins, fluoroquinolones, cephalosporins, macrolides, and tetracyclines are the most commonly used. Each drug within a class has its own unique properties.

Penicillin is an important antibiotic for paediatric patients, but it is the most common drug allergy trigger, according to the Asthma and Allergy Foundation of America12. Up to 10% of all people report an allergy to penicillin. Many children who are allergic to penicillin may also be allergic to cephalosporin, according to a study published in Pediatric Allergy Immunology, which showed that 31.5% of the penicillin allergic children in the study cross-reacted to some cephalosporin13. Hypersensitivity to penicillin is also an issue for newborns, in that it may cause nausea, vomiting, pruritis, urticaria, wheezing, laryngeal edema and, ultimately, cardiovascular collapse in these very young patients14.

Antimicrobial dosages for neonates Prescribing for neonates is different than for adults. Extracellular fluid constitutes up to 45% of total body weight in neonates, so these young patients require relatively larger doses of certain antibiotics, especially aminoglycosides, as compared with adult patients. Premature infants may present lower serum albumin concentration, which may reduce antibiotic protein binding. Sulfonamides, ceftriaxone and other drugs that displace bilirubin from albumin can increase the risk for kernicterus.

Neonates may present an absence or deficiency of certain enzymes, which can prolong the half-life of chloramphenicol and other antibiotics. Changes in renal tubular secretion and glomerular filtration rate during the first month of life require changes in dosing for penicillins, aminoglycosides, vancomycin, or other antimicrobial drugs.

Antimicrobial stewardship in paediatric care

Antimicrobial therapy is one of the most widely used therapeutic approaches to paediatric care available today. Unfortunately, the use and misuse of antimicrobials – especially antibiotics – has fuelled an expansion of antibiotic-resistant microbes. This resistance to antimicrobials is making these “miracle drugs” less effective.

Paediatric patients now face increasing uncertainty as to whether tomorrow’s microbial infections may become resistant to today’s antimicrobial therapies. To avert this disaster, it is incumbent upon practitioners to limit antimicrobial therapy to only those paediatric cases that warrant it. Many paediatricians and other clinicians face a great deal of pressure from patients and parents to prescribe antibiotics. It is often helpful for a practitioner to provide educational materials and explain how the risks of antibiotics sometimes outweigh the benefits. Practitioners should include parents in the development of a treatment plan, which may include analgesics or decongestants where appropriate, and provide a realistic time course for resolution.

It is also essential to understand the importance of antimicrobial stewardship, to know when to consult an infectious disease specialist for guidance in a case, and to be able to identify cases where the patient does not need antimicrobial therapy. General guidelines help clinicians provide antimicrobial therapy to paediatric patients in a responsible manner that benefits the child and the community.

REFERENCES

1. http://www.ncbi.nlm.nih.gov/ pubmed/16054422
2. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3944165/
3. http://comprped.com/?page=article&article_id=10273
4. http://www.ncbi.nlm.nih.gov/ pubmed/24167170
5. http://www.medscape.com/ viewarticle/729287
6. http://pediatrics.aappublications.org/content/ early/2013/09/18/peds. 2013-1112.abstract
7. http://www.ncbi.nlm.nih.gov/ pubmed/19824881
8. http://jac.oxfordjournals.org/content/61/ suppl_1/i35.long
9. http://www.drugs.com/drug-class/polyenes. html
10. http://www.medscape.com/ viewarticle/545478_11
11. http://pediatrics.aappublications.org/content/ 129/5/1006.full
12. http://www.aafa.org/display. cfm?id=9&sub=30
13. http://www.ncbi.nlm.nih.gov/ pubmed/15943598
14. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3255391/

 Date of upload: 21st Jul 2015

 

                                  
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