Vancomycin is an antibiotic glycopeptide that was isolated of the Streptomyces orientalis. It was introduced in the clinical practice for treatment of infections caused by staphylococcus in which other antibiotics were proving to be ineffective. In this retrospective study, we determine its prescription, clinical characteristics as well as the factors that favor the apparition of the erythroderma or red-man syndrome in a paediatric hospital. Forty patients to which physicians administer vancomycin and presented erythroderma were evaluated. Male gender was more predominated, with a total of 25 cases (62.5 %). The average age was of 12 ± 6 years. We identified two main factors that are directly related to the appearance of erythroderma. On one hand, the "concentration of the drug", which is related to the dilution that it is realized when a dose of vancomycin is going to be administered to the patient and on the other hand the “time or speed of infusion”. In the present study, it was found a low incident of this adverse reaction and few cases of complications.
Key words: Erythroderma; Adverse Reactions; Vancomycin, Pharmacovigilance; Children.
Vancomycin is a glycopeptide antibiotic that was isolated in 1956 from Streptomyces orientalis. It was introduced into clinical practice in 1958 for treatment of infections caused by staphylococci, in which other antibiotics proved ineffective. Vancomycin began to be used more significantly in the seventies of the last century, but it was not until the eighties when the prescriptions increased considerably due to the emergence of strains of Staphylococcus aureus resistant to methicillin in hospitals.1-10
Vancomycin is active against gram-positive organisms, particularly against staphylococci (including methicillin-resistant) and streptococci. Vancomycin is administrated intravenously in the treatment of systemic infections (as oral absorption is poor). Intramuscular administration of vancomycin is not recommended because it causes intense pain and necrosis. The main adverse reactions of vancomycin are ototoxicity and nephrotoxicity. However, intravenous administrations is able to produce phlebitis, erythroderma, also known as the red man syndrome (RMS) or as exfoliative dermatitis (it is defined as a generalized redness and scaling of the skin), among others.1-19 Erythroderma has been described extensively in adults and children, even in infants (from one month to one year) and neonates. Nevertheless, existing information is scarce and limited to few cases.4-19 Incidence of erythroderma in pediatrics has been established to be from 1.5 to 7.3%.10, 11
Erythroderma is frequently characterized by muscle or maculopapular rash on the neck, face, upper chest and upper limbs. Erythroderma may also affect large areas of the body and lower limbs. Likewise, alterations of the cardiac rhythm may be produced by the drug. Patients may present hyperthermia, hypotension, pruritus and erythematous rash mainly on the face, neck and back. In infants, the rash is associated with decreased tissue perfusion, cold extremities, increased oxygen requirements and letargia.7-20 Pharmacovigilance must be realized to the administration of drugs in children on hospitals, for this reason we chose to study the adverse reactions to the vancomycin intravenous injection in patients in a pediatric Hospital.
A descriptive, retrospective, observational study was administered to determine the frequency and factors favoring the appearance of erythroderma after intravenous vancomycin in patients in a pediatric Hospital. Ethics and Investigation Committees approved the study protocol and the study was performed according to the guidelines delineated by the Declaration of Helsinki and the rules of the Ley General de Salud. Relevant data for this study were collected through the review of the adverse reaction reports to vancomycin from 2009 to 2010. All patients (all ages, both genders and any diagnostic) with report of erythroderma following intravenous administration of vancomycin were included. Data were entered into a computerized database. The SPSS version 17 for Windows (SPSS Inc., Chicago, IL, USA) was used for descriptive analyses.
Forty reports of erythroderma were included, of which there were 24 cases in 2009 and 16 in 2010, thus establishing a higher incidence of cases in 2009. The gender in which this reaction was more predominant was male gender, with a total of 25 cases, equivalent to 62.5%, and 15 female patients, equivalent to 37.5%. Mean age was 12 ± 6 years (Table 1).
Among the factors that are directly related to the occurrence of erythroderma as an adverse reaction, (which are essential to trigger this reaction) is the "drug concentration", which is related to the dilution that takes place when a dose of vancomycin is administered and the “infusion rate or speed” with which the drug passes to a patient. In the present study, higher concentrations of this drug were given at shorter time than recommended (Table 2). In this sense, it has been established that the diluted minimum concentration of this antibiotic for its administration is of 5 mg/mL, as well as the time of infusion must not be less than an hour or more. According to the medical specialties, 17 patients were of internal medicine, 14 patients in oncology, 4 patients in the pediatric intensive care unit, 2 patients in neonatal intensive care unit, 2 patients the emergency room and 1 patient in the infant’s service.
In the present study, the majority of cases (87.5%) of erythroderma was related to a “short infusion rate” and “lack of dilution” in the administration of vancomycin, both is able to produce adverse reactions.11-29 Only five patients had a dilution and infusion rate correct. Previous studies have shown a relationship between the release of histamine and the amount of histamine in plasma after the vancomycin administration.4, 8, 9, 25-27 Because of the relationship between vancomycin administration and the onset of erythroderma, the medical staff responsible for the administration of medications should pay more attention in the care of pediatric patients receiving intravenous vancomycin. Likewise, medical staff should know the signs and symptoms of this reaction, as well as the concentration at which vancomycin must be diluted at a ratio of at least 5mg/mL and an infusion rate of no less than 60 minutes. Also, the patients should be carefully monitored, as the adverse reaction may occur even with a slow infusion rate.17-25 Pharmacovigilance intensive should be performed when vancomycin is administered to a patient with the antecedent of erythroderma previous, recommending a slower infusion rate and premedication with antihistamines (H1) with or without corticosteroides.12-29 Measures to improve detection and reporting of erythroderma by all health care professionals should be undertaken, to enhance our understanding of the nature and the medical and economic impact of this reaction in children.
| Age (years) | 2009 n (%) |
2010 n (%) |
| 0-5 | 5 (20.8) | 3 (18.7) |
| 6-13 | 17 (70.8) | 11 (68.7) |
| >13 | 2 (8.3) | 2 (12.6) |
| TOTAL | 24 (100) | 16 (100) |
Table 1. Age distribution of the population with erythroderma.
| Prescribed dose (mg) | Concentration in the dilution that was administered (mg/ml) | Infusion rate during the administration (minutes) | n (%) |
| 25 – 50 | 10 mg/mL | 30 | 6 (15.0) |
| 51 – 100 | 12 mg/mL | 30 | 5 (12.5) |
| 101 – 200 | 18 mg/mL | 30 | 13 (32.5) |
| 201 – 300 | 20 mg/mL | 60 | 11 (27.5) |
| 301 – 400 | 4 mg/mL | 60 | 3 (7.5) |
| >400 | 4 mg/mL | 120 | 2 (5.0) |
Table 2. Vancomycin administration in patients at the paediatric hospital.
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[*]Hospital del Niño DIF, Pachuca de Soto, Hidalgo, México