Question

Critical Thinking Questions for Submissions: # 4

1. Why are quinolones not recommended in children under the age of 12.
2. Discuss the indications of the use of Ivermectin in the pediatric population. What important information should be given to the patient/parent/guardian?
3. When are macrolides most commonly used as the drug of choice? please show your citation

Answer 1

• Why are quinolones not recommended in children under the age of 12.

Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use.

In the use of medications particularly antibiotics in pediatric patients, it is imperative to remember that pharmacokinetic and pharmacodynamic processes may be different in children compared with adults. These physiological changes can result in unfavorable outcomes for the pediatric patient. Here we are focusing on the use of antibiotic historically contraindicated in children: fluoroquinolones

Controversy: Fluoroquinolones have demonstrated adverse effects on cartilage development in juvenile animals through the inflammation and destruction of weight-bearing joints. These arthropathies were often irreversible, and their potential occurrence in children limited the use of fluoroquinolones in this population. In one pediatric study, ciprofloxacin had a 3.3% (9.3% vs. 6.0%) absolute risk increase in musculoskeletal events within 6 weeks of treatment compared with control agents used to treat complicated UTIs or pyelonephritis. Adefurin and colleagues found a 57% increased relative risk of arthropathy in children given ciprofloxacin (21% overall) versus those in a nonfluoroquinolone comparator arm. In contrast to animal models, neither dose nor duration had an effect on the rate or severity of arthropathy. A 2007 study by Noel and colleagues determined the incidence of musculoskeletal events (primarily arthralgias) to be greater in children treated with levofloxacin compared with nonfluoroquinolone-treated children at 2 months (2.1% vs. 0.9%; P = .04) and 12 months (3.4% vs. 1.8%; P = .03). These results and the severity of the effects should be weighed heavily when initiation of fluoroquinolones is being contemplated in pediatric patients.

Another significant concern with fluoroquinolone use is increased bacterial resistance. Resistance patterns to fluoroquinolones, which have consistently worsened in adults over the last 20 years, can occur via multiple mechanisms, such as changes in target enzymes (DNA gyrase and DNA topoisomerase) or the expression of efflux pumps. The synthesis of newer fluoroquinolones, such as moxifloxacin, created expectations that resistance to gram-positive bacteria would be limited. However, resistance is often considered a class effect and may become a significant concern in the pediatric population with continued use.

Potential Benefits: Fluoroquinolones have been used successfully in a variety of pediatric infections, including cystic fibrosis exacerbations, complicated UTIs, and otitis media. Use in children with neutropenic fever or multidrug-resistant gram-negative infections has also increased. However, most of the literature supporting the use of fluoroquinolones in children comes from retrospective or small, uncontrolled studies.

Evidence of fluoroquinolone-induced arthropathies in pediatric patients is well documented, but no cases of clinician-diagnosed cartilage destruction in children have been noted in either controlled clinical trials or unsolicited FDA reports. Additionally, one retrospective study involving more than 20,000 children demonstrated no significant difference in joint or tendon disorders with fluoroquinolones versus azithromycin. Although fluoroquinolones carry a black box warning regarding tendon rupture, there are no published reports of this adverse event in children.

Regarding fluoroquinolone resistance, the overall resistance pattern in pediatric gram-negative isolates (excluding cystic fibrosis patients) has been documented at less than 5%. However, it is likely that resistance rates will rise with increased pediatric fluoroquinolone use.

• Discuss the indications of the use of Ivermectin in the pediatric population. What important information should be given to the patient/parent/guardian?

Ivermectin is a medication used to treat many types of parasite infestations. This includes head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis. It can be taken by mouth or applied to the skin for external infestations. Use in the eyes should be avoided.

Contraindication

Children, infants, neonates

Ivermectin oral tablets are approved for use in children >= 15 kg of weight. Safe and effective use has not been established in neonates, infants or children weighing less than 15 kg. The topical administration of ivermectin to children should be under the direct supervision of an adult to prevent ingestion of the lotion and/or cream. The safety and efficacy of ivermectin lotion have not been established in neonates or infants < 6 months. Topical ivermectin lotion is not recommended in pediatric patients < 6 months because of the potential for increased systemic absorption due to a ratio of skin surface area to body mass. There is also a potential increased risk of ivermectin toxicity due to an immature skin barrier. The safety and efficacy of ivermectin cream have not been established in children < 18 years of age.

For the treatment of pediculosis including pediculosis capitis, pediculosis corporist, and pediculosis pubist.

Topical dosage (lotion)

Infants 6 months and older, Children, and Adolescents

Apply a sufficient amount of lotion (up to 1 tube) to thoroughly coat dry hair and scalp for pediculosis capitis. Leave on for 10 minutes then rinse off with water. A fine-tooth comb or special nit comb may be used to remove dead lice and nits. Wait 24 hours before applying shampoo to hair and scalp after use.

MAXIMUM DOSAGE

Children

> 15 kg: 150—200 mcg/kg single dose PO for most indications; 4 oz/topical application.
<= 15 kg: Safety and efficacy have not been established for oral dosage forms; 4 oz/topical application.

Infants

>= 6 months: Safety and efficacy have not been established for oral dosage forms; 4 oz/topical application.
< 6 months: Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

ADMINISTRATION

Oral Administration

Oral Solid Formulations

Administer ivermectin tablets on an empty stomach with water.

Topical Administration

Cream/Ointment/Lotion Formulations

Ivermectin lotion
Ivermectin lotion is administered topically for head lice. Avoid contact with eyes, mouth, or any mucus membrane. Do not ingest.
Scalp and hair should be dry prior to application.
Apply a sufficient amount to thoroughly cover scalp and hair (up to the full contents of 1 tube).
Leave on for 10 minutes, and then rinse with only water.
Wash hands after use.
Wait 24 hours before applying shampoo to hair and scalp after use.
The tube is for single use only; discard any unused portion.
For proper treatment of pediculosis, wash in hot water or dry clean all recently worn clothing, hats, used bedding and towels, and wash personal care items such as combs, brushes, and hair clips in hot water.
Ivermectin cream
Ivermectin cream is administered topically for rosacea. Avoid contact with eyes and lips.
It is not for oral, ophthalmic, or intravaginal use.
Apply to the affected areas of the face.

• When are macrolides most commonly used as the drug of choice? please show your citation

Alternative to penicillin

Macrolide antibiotics can also be used as an alternative to penicillin antibiotics. They are often prescribed for people who are allergic to penicillin.

Macrolide antibiotics are a particular type of antibiotic used to treat, and sometimes prevent, a wide variety of bacterial infections. First-line indications for macrolides include the treatment of atypical community acquired pneumonia, H. Pylori (as part of triple therapy), chlamydia and acute non-specific urethritis. Macrolides are also a useful alternative for people with penicillin and cephalosporin allergy.

Macrolides have been considered the drug of choice for group A streptococcal and pneumococcal infections when penicillin cannot be used. However, pneumococci with reduced penicillin sensitivity are often resistant to macrolides, and in some communities, up to 20% of S. pyogenes are macrolide-resistant.

How they work

Macrolide antibiotics stop bacteria multiplying by preventing them from being able to produce proteins that are essential for their growth. The bacteria eventually die or are killed by your immune system.

Names

Macrolide antibiotics are:

• azithromycin (brand name Zithromax),
• clarithromycin (brand names Klacid and Klacid LA),
• erythromycin (brand names Erymax, Erythrocin, Erythroped and Erythroped A),
• spiramycin (no brand), and
• telithromycin (brand name Ketek).

Uses of macrolide antibiotics

Treatment

Macrolide antibiotics are only effective in treating bacterial infections associated with the following conditions:

• Ear, nose and throat infections - such as otitis media (infection of the middle ear), labyrinthitis (infection of the inner ear), sinusitis (infection of the sinuses), tonsillitis (infection of the tonsils) and laryngitis (infection of the voice box).
• Chest infections - such as pneumonia (infection of the lining of the lung), bronchitis (infection of the airways of the lung) and whooping cough.
• Skin infections - such as eczema, psoriasis or acne that has become infected.
• Mouth and dental infections - such as gingivitis (infection of the gums) and a tooth abscess (infection in the root of a tooth).
• Sexually transmitted infections - such as chlamydia.

Prevention

Macrolide antibiotics may also be prescribed to prevent certain types of bacterial infection.

For example, if you have sickle-cell disease, or have had your spleen removed (splenectomy), you may need to regularly use antibiotics to prevent infections.

Also, if you have undergone any type of dental procedure and are at risk of endocarditis (infection of the heart lining and valves), you may need to take a course of antibiotics. Speak to your dentist and GP before any procedure for further advice.