Çocukluk Çağında Vankomisin Kullanım Endikasyonlarının ve Olası İstenmeyen Etkisinin Ortaya Çıkışına Etki Eden Faktörlerin Değerlendirilmesi

Abstract

Vancomycin has been a first-line antibiotic for resistant Gram-positive microorganisms, such as methicillin-resistant Staphylococcus aureus (MRSA), since the 1960s. In recent years, the increasing beta-lactam resistance in microorganisms has heightened the importance of vancomycin use. Concerns about its side effects contribute to the hesitancy in employing vancomycin as the first choice in treatment. Our study retrospectively examined 1378 pediatric patients admitted to Hacettepe University İhsan Doğramacı Children's Hospital between January 2019 and December 2021, who received vancomycin for the treatment of infectious diseases. Of these cases, 592 (43%) were female, and 786 (57%) were male, with a median age of 4.46 (1.22-10.10) years. A total of 171 (12.4%) patients had weight above the 95th percentile for age and gender. The median duration of treatment was 11 (7-15) days, with 884 (64.2%) cases receiving empirical therapy being the most common indication. Vancomycin was initiated in 242 (17.6%) cases due to neutropenic fever, 152 (11.0%) cases with resistant microorganisms, and 100 (7.3%) cases with catheter-related infections. The most common type of infection was suspected bacteremia (358, 26%), followed by pneumonia (317, 23%), meningitis (181, 13.1%), and skin and soft tissue infections (158, 11.5%). The accuracy of indication according to the CDC (Centers for Disease Control and Prevention) was found to be 66.8%. Microbiological agents were identified in 575 (41.7%) cases, with 494 bacteria and 381 Gram-positive microorganisms. Among 330 isolates tested for methicillin resistance, 43.7% exhibited methicillin resistance in S. aureus strains, with a prevalence of 31.7% for community-acquired MRSA and 56.5% for healthcare-associated MRSA. The highest methicillin resistance was observed in S. epidermidis, with 90.5% resistance among 116 strains. In our study, no vancomycin-resistant organisms were found except for one S. epidermidis strain with intermediate susceptibility to vancomycin. Adverse effects were observed in 211 (15.3%) cases, with a median duration of 4 (1-13) days. The incidence of drug-related side effects increased over the study duration. Among 66 patients who had previously experienced vancomycin side effects, re-administration resulted in no recurrence in 53 (80.3%) cases. In 45 patients experiencing side effects during treatment, vancomycin was continued, and side effects did not recur in 34 (75.6%) cases. The frequency and distribution of side effects were as follows: hypersensitivity in 70 (5.2%) cases, peripheral complications in 68 (5%) cases, nephrotoxicity in 29 (2.2%) cases, cytopenia in 28 (2.1%) cases, fever in 20 (1.5%) cases, hepatotoxicity in 11 (0.8%) cases, and thrombophlebitis in 1 (0.1%) case. There was no evidence of ototoxicity in any patient. Among the 70 cases with hypersensitivity, 35.7% had urticaria, 30% had exfoliative dermatitis, 14.3% had anaphylaxis, 7.1% had DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), 5.7% had vasculitis, 2.9% had angioedema, 2.9% had vascular collapse, and 1.4% had Steven-Johnson Syndrome. Peripheral intravenous (IV) side effects occurred in a total of 68 cases. "Red man" syndrome occurred in 63 cases (92.7%), being the most common peripheral IV side effect. Among those experiencing peripheral IV or hypersensitivity reactions, treatment duration was increased in 43 cases, antihistamines were administered 52 times, steroids were given 19 times, inotropes were administered 3 times, and saline loading was done 2 times. Among the 44 patients with peripheral side effects or hypersensitivity reactions, treatment was continued in 44 cases, and only 10 (22.7%) experienced ongoing side effects, leading to discontinuation of the drug. Fluid support resulted in fewer hypersensitivity and peripheral side effects. As the vancomycin dose per body weight increased, side effects increased, with the highest increase observed in peripheral IV complications. Hypersensitivity and peripheral reactions were less common in patients receiving furosemide and dopamine, where the dose per body weight was lower. The frequency of fever and drug-induced cytopenia was higher when observed together. The co-administration of vancomycin with clindamycin led to a significant increase in fever, hepatotoxicity, and cytopenia. Hypersensitivity and peripheral reactions were generally observed at the beginning of treatment, while cytopenia and hepatotoxicity were observed later. Based on initial serum creatinine levels, of the 1083 patients, 154 (12.5%) had an increase in creatinine values by more than 1.5 times at the end of treatment. The use of nephrotoxic drugs and antibiotics was associated with more frequent creatinine increases and nephrotoxicity. According to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, kidney damage was more common with vancomycin plus piperacillin-tazobactam, fluconazole, amphotericin B, ciprofloxacin, trimethoprim-sulfamethoxazole, acyclovir, ganciclovir, and clarithromycin. Additionally, kidney damage was more common when vancomycin was used with paracetamol, dopamine, vasopressors (excluding dopamine), furosemide, and G-CSF (Granulocyte Colony-Stimulating Factor). Nephrotoxicity was more frequent when vancomycin was administered with piperacillin-tazobactam, amikacin, trimethoprim-sulfamethoxazole, and clarithromycin, correlating with an increase in creatinine levels. An increase in GGT was observed with meropenem, amikacin, and ciprofloxacin, while an increase in ALT, AST, and GGT was observed with fluconazole. Particularly, those who used cefazolin in the last three months had a more frequent increase in GGT.