There is a cumulative evidence suggesting COVID-19 victims are prone to COVID-19 associated pulmonary aspergillosis (CAPA).COVID-19 itself and immunomodulatory medications, such as corticosteroids and tocilizumab, compromise the immune system to an extent that opportunistic infections complicate the course further. 1 In this letter, we aimed to highlight the relationship between inflammation and voriconazole trough levels in COVID-19 patients.Voriconazole is recommended as the first-line agent for the treatment of invasive pulmonary aspergillosis (IPA). 1 Voriconazole is metabolized with cytochrome P450 (CYP450) isoenzymes (mainly with CYP2C19 and lesser extent with CYP3A4) to voriconazole Noxide. Voriconazole reaches to steady-state trough concentrations approximately at the fifth day of administration. Therapeutic drug monitoring for voriconazole is recommended because of the narrow therapeutic index. 2 Voriconazole dose for IPA is recommended as 4 mg/kg every 12 h for maintenance, followed by 6 mg/kg loading dose every 12 h in the first day. It was recommended that the trough level of voriconazole should be between 1.5 and 5.5 mg/L. Voriconazole trough level over 4.5-6 mg/L has been associated with hepatotoxicity. 3 The common side effects of voriconazole were defined as visual disturbances, fever, nausea, rash, vomiting, chills, headache, abnormal liver function tests, and hallucinations. 4 Since the beginning of COVID-19 pandemic, a total of 13 COVID-19 patients were treated with voriconazole for CAPA in our university hospital based on mycological, clinical, and radiological findings. Among 13 patients, 12 (92.3%) were critically ill. All patients, except one, had bacterial or viral coinfection in addition to CAPA.Plasma voriconazole level measurements were performed with liquid chromatography-triple quadrupole mass spectrometer (Shimadzu LCMS-8040). Two of those had a DDI with voriconazole (with 500-mg intravenous clarithromycin twice daily and 80-mg oral omeprazole daily), which might contribute to high voriconazole trough levels due to their inhibitory effect on CYP450 isoenzymes. However, the voriconazole level remained elevated despite discontinuation of clarithromycin in one patient, suggesting a different mechanism. In five (41.7%) critically ill patients, the trough level of voriconazole remained in the supratherapeutic range despite a dose reduction of 100 mg/day. In summary, no associated factor was detected for the explanation of higher voriconazole trough levels in 12 critically ill patients. It was observed that COVID-19 patients were more prone to high voriconazole levels than non-COVID-19 patients. In four of 13 non-COVID-19 patients, the voriconazole trough level was

Carbapenems have a beta-lactam ring that might prone to cause hypersensitivity reactions. We proposed that the clinical cross-reactivity between the individual carbapenems will develop independently from the betalactam ring in this case report. A 75-years-old male patient was admitted to the surgical intensive care unit after whipple procedure for malignant neoplasm of the pancreas. Meropenem and colistin was started because of increased oxygen demand. Most likely drug-induced generalized maculopapular skin rash developed on the first day of the antimicrobial therapy. Followed by discontinuation of meropenem, imipenem-cilastatin therapy was administered without any problem. Because of the increase in the existing infiltrate on the chest x-ray, ertapenem was added as a double-carbapenem strategy. However, it has been discontinued after one dose due to appearing same adverse effects with meropenem. Besides, the lack of allergy history despite prior ceftazidime usage implies that the hypersensitivity reaction of the patient was unlikely related to the beta-lactam ring.

Obesity is closely associated with a great number of infectious diseases. Certain challenges are experienced in the management of these infections due to the physiological changes in obese individuals. These physiological changes lead to alterations in pharmacokinetics and pharmacodynamics profiles of antimicrobial drugs. In terms of pharmacokinetics, the volume of distribution and the clearance of the drug; with regard to pharmacodynamics, the minimum inhibitory concentration and area under the curve play an important role in drug treatment. Consequently, administration of drug doses which are applicable to normal weight patients causes either inadequate treatment or undesirable outcomes such as nephrotoxicity and hepatotoxicity in obese patients. Since the drug dosing (per kilogram dose) is based on the actual body weight, appropriate changes in the doses of certain drugs may be required. A number of descriptive measurements for body size-total body weight, lean body weight, adjusted body weight, ideal body weight, body mass index, body surface area-have been developed and formulated for this. The method to be used for obese individuals is determined in accordance with the physicochemical properties of a particular drug. This review aimed to investigate pharmacokinetic and pharmacodynamic changes in obese patients and to provide up-to-date information on dose changes that might be required to administer accurate and rational doses of antibiotic, antifungal and antiviral drugs, and also to indicate which body size measurement should be used during drug treatment.

Three formulations of amphotericin B are available: liposomal, lipid complex and conventional. The liposomal amphotericin B is more preferred agent than other formulations because of its tolerability, safety and potent antifungal activity. However, the liposomal amphotericin B can cause infusion-related reactions. In this case report, we aimed to report a patient who developed infusion-related reactions during the treatment with the liposomal amphotericin B but eventually tolerated the prolonged infusion. In this case report, we present a patient who developed an infusion-related reaction during The liposomal amphotericin B treatment. A 26-year-old male patient with acute promyelocytic leukemia was hospitalized for the third course of chemotherapy. Due to the invasive fungal infection history in previous hospitalizations, the liposomal amphotericin B 400 mg (IV, 5 mg/kg) once daily was initiated as secondary antifungal prophylaxis. Swelling in infusion site and chest pain were reported within 10 minutes of the liposomal amphotericin B administration, and the infusion rate was slowed down to 400 mg/6 hours from 400 mg/2 hours. All these reactions disappeared with prolonged infusion time. The patient received a total of 7 liposomal amphotericin B doses subsequently without any reaction during the chemotherapy cycle. In our experience, the liposomal amphotericin B-induced infusion-related reactions can be resolved by prolonging the infusion time.

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