Adverse effects of vancomycin in children : a review of 22 cases

Vancomycin is a polypeptide antibiotic isolated in 1956 and introduced into medicaI practice in 1958, for treating infections caused by penicillinresistant staphylococci.1 It has many mechanisms of action, the best known and probably most important being the inhibition of cell wall synthesis in bacteria.2 In addition to being extremely effective against Gram-positive bacteria,3-5two features of vancomycin are of great interest in medicaI practice: the low leveI of bacterial resistance to the antibiotic, and the negligible -incidence of cross reactions with other antibiotics. Initial preparations of vancomycin contained many impurities frequently associated with adverse effects. Today, with drug purification, the number of patients who experience toxic effects is very small. Furthermore, wellcontrolled drug administration, according to technical

standards, has also contributed to a reduction in the incidence of adverse effects.
After intravenous administration, vancomycin is distributed into various body fluids.Many factors influence the drug's pharmacodynamics, including age.Total body clearance of vancomycin increases with age.Due to the complex pharmacokinetics of the drug, the monitoring of the antibiotic concentration in plasma is recommended to assure successful therapy.[6][7][8][9] The main adverse effects associated with vancomycin are: 10-12

•
Histamine-like reaction, commonly seen as flushing and a maculo-papular rash of the face, neck, upper thorax, back and arms.The reaction may affect the entire body surface and be accompanied by itching, paresthesia, dizziness, fever, chest pain and edema of the face, lips, and eyelids.More severe symptoms such as tachycardia or bradycardia and, more rarely, systemic arterial hypotension or shock, may be observed;  The drug was prepared for intravenous administration at a concentration of 5 mg/ml.The dosage used was 15 mg/kg/dose over a 60-minute period, every 6 hours.
Measurements of plasma concentration of vancomycin were taken at maximal and minimal concentration leveIs of the phase of equilibrium, that is, after the second day of therapy.Plasma concentration was determined by poIarized immunofluorescence on TDx equipment.As plasma concentrations presented great individual variation, leveIs of 30 to 40 mcg/ml at maximal, and below 10 mcg/mI at minimal were considered adequate.9 Optimum plasma leveIs were observed in only eight children.
Hemogram, urea and creatinine concentration, serum transaminase leveIs and urinanalysis were performed at the beginning of therapy and weekly during treatment in order to monitor adverse effects.Ototoxicity was not evaluated.Concomitant therapy with a cephalosporin or aminoglycoside was necessary in 14 cases.
Nine adverse effects observed in six children are described in the Table .Changes in plasma urea and creatinine leveIs upon introduction of vancomycin therapy did not occur.
The following adverse effects were observed: two cases of skin rash (9.1 percent), five episodes of eosinophilia (22.7 percent), and two cases of increase in serum creatinine concentration (9.1 percent).
Skin rashes were observed during drug infusion, and after the second week of treatment.
Eosinophilia was defined as the number of eosinophils above 500 cells/ ml, and was observed after the second week of treatment in five cases.
Remission occurred after the end of treatment.Changes in plasma creatinine were observed during the second and third weeks of treatment.Twofold or greater increases were considered significant.
Both cases with an increase in plasma creatinine concentration 29.9Although increase in serum bilirubin has been associated to the use of vancomycin, there is no clear proof of hepatoxicity; 10 Arterial hypertension has been described recently, aIthough hypotension is the cardiovascular effect most frequently observed.
The Children ~s Institute of the Hospital das Clinicas of the University of São Paulo, a major tertiary hospital, treats children with chronic anel/or severe diseases in which immunodepression, the use of invasive procedures, and frequent hospital admissions often lead to the development of multi-resistant Gram-positive bacterial infections.Vancomycin plays an important role in the treatment of these infections.
Therefore, we followed 22 children in whom vancomycin was clinically indicated for treating severe infections caused by suspected Case 1 or confirmed multi-resistant Case 2 staphyIococci.
We observed possibIe adverse effects of the occurred with simultaneous use of other drug's, in one case amycacin, and in another, ceftriaxone.Creatinine plasma leveIs returned to normal after the drugs were withdrawn.
Serum concentrations above 40mcg/ml occurred in two of the six children who suffered adverse effects, and in four children the serum concentrations were below 40 mcg/ml.
From the analysis of the data above we can conclude that: • • Plasma concentrations presented great individual variation, confirming that the recommended dosage of vancomyci~is suitable for initial therapy, but serum concentrations should be monitored to adjust dosage; Significant adverse effects were not observed during infusion, suggesting that administration standards have a protective role; Adverse effects were transient and remitted after vancomycin was withdrawn.