Investigation of polypharmacy, antimicrobial-related potential drug-drug interactions in patients with hematological malignancies.

PURPOSE: Drug-drug interactions (DDIs) occur when one drug interferes with the pharmacological activity of another and can lead to increased side effects. The purpose of this study was to examine potential interactions between antimicrobials and other drugs in patients with hematological malignancies (HMs). METHOD: The medications used by 233 patients with HMs before and during hospitalization in Ankara City Hospital Hematology Clinic services between January 2021 and July 2021 were examined. Potential DDIs (pDDIs) were identified through UptoDate, Drugs.com, and MedScape databases. The effects of major antimicrobial-related pDDIs on patients were examined. Agreement between the two interaction systems was judged based on the kappa test. SPSS R Version 4.0.2 was used in the statistical analysis of the data, p<.05 was considered significant. RESULTS: The prevalence of polypharmacy before hospitalization was determined as 22.7%. Diagnosed with acute leukemia and multiple myeloma, more antimicrobial-related pDDIs were detected during hospitalization (p<.001). A total of 758 antimicrobial-related pDDIs, which were in the major category in at least one of the three databases, were detected in 72.5% (169/233) of the participants. It was determined that the total hospitalization period of patients with major antimicrobial-related pDDIs was longer (p<.001). There was negligible agreement between UptoDate and Dugs.com and between Drugs.com and MedScape (kappa: 0.008 for both). There was no compatibility between UptoDate and MedScape (kappa<0). CONCLUSION: Interactions between antimicrobials and other drugs are undesirable problems. Further studies are required to evaluate the clinical and economic effects of the interactions on patients with HMs.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BACKGROUND: The development of candidemia is a highly fatal condition in severe COVID-19 infection. OBJECTIVES: This study aimed to develop a candidemia prediction score in COVID-19 patient based on the patient's clinical characteristics, and healthcare-related factors during intensive care units (ICU) follow-up. PATIENTS/METHODS: Severe COVID-19 patients hospitalised in ICU in Ankara City Hospital during the one-year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score. RESULTS: Of 1305 COVID-19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12-44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39-3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42-5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34-0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81-0.87). CONCLUSION: We developed and validated an easy-to-use clinical prediction score for candidemia in severe COVID-19 infection. In COVID-19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Incidence and risk factors for COVID-19 associated candidemia (CAC) in ICU patients.

BACKGROUND: Critically ill COVID-19 patients have a high risk for the development of candidemia due to being exposed to both well-defined classical risk factors and COVID-19-specific risk factors in ICU. OBJECTIVES: In this study, we investigated the incidence of candidemia in critically COVID-19 patients, and the independent risk factors for candidemia. PATIENTS/METHODS: COVID-19 patients hospitalised in ICU during 1-year period (August 2020 to August 2021) were included. Clinical and laboratory characteristics of all COVID-19 patients, applied treatments, and invasive procedures that may predispose to candidemia were recorded. RESULTS: Of 1229 COVID-19 patients, 63 developed candidemia. Candidemia incidence rate was 4.4 episodes per 1000 ICU days. The most common species was Candida albicans (52.3%). Only 37 patients (58.7%) received antifungal therapy. The presence of central venous catheter (OR 4.7, 95% CI 1.8-12.2, p < .005), multifocal candida colonisation (OR 2.7, 95% CI 1.4-5.2, p < .005), a prolonged ICU stay (≥14 days) (OR 1.9, 95% CI 1.08-3-37, p < .05), the absence of chronic lung disease (OR 0.4, 95% CI 0.1-0.9, p < .05) and the absence of corticosteroid use (OR 0.3, 95% CI 0.14-0.52, p < .0001) were significantly associated with candidemia. CONCLUSIONS: Our study filled the knowledge gap in the literature about the impact of COVID-19-associated risk factors for the development of candidemia. The classical risk factors for candidemia had a significant effect on candidemia, and contrary to expectations, corticosteroids had a protective effect against the development of candidemia. The results of these studies showing interesting effects of corticosteroids in critically ill COVID-19 patients should be confirmed by further studies.

Increasing rates of extended-spectrum B-lactamase-producing Escherichia coli and Klebsiella pneumoniae in uncomplicated and complicated acute pyelonephritis and evaluation of empirical treatments based on culture results.

Increasing rates of extended-spectrum beta-lactamase (ESBL) producing E. coli and K. pneumoniae over time made empirical treatment complicated. Knowing local antimicrobial resistance patterns of common pathogens can make it easier to decide on empirical antibiotics. We aimed to investigate the prevalence and risk factors of ESBL positivity of E. coli and K. pneumoniae strains in uncomplicated and complicated pyelonephritis acquired in community and healthcare associations and to evaluate the appropriateness of empirical treatment. Adult patients hospitalized with diagnosis of community-acquired or healthcare-associated uncomplicated/complicated pyelonephritis initiated empirical antimicrobial therapy were included in the study. Appropriateness of empirical treatment at 48-72 h based on culture results and treatment modifications were evaluated. A total of 369 uncomplicated (94) and complicated (275) episodes of pyelonephritis were evaluated. The most common agents were E. coli (71.0%) and K. pneumoniae (17.7%), and the ESBL-production rate was 64.4%, and higher in healthcare-associated pyelonephritis (P 0.013). Being of healthcare-associated infection, previous antibiotic use, and presence of urinary catheters were independent risk factors for ESBL-producing E. coli and K. pneumoniae (P 0.009, < 0.001, and 0.024, respectively). The treatment inappropriateness was mostly associated with use of ceftriaxone (56.3%) (P < 0.001). Treatment has escalated in 41.5% of ceftriaxone-initiated patients, in only 8.8% and 9.5% ertapenem and piperacillin-tazobactam-initiated patients, respectively. ESBL-production rates are quite high even in community-acquired infections. The use of broad-spectrum antibiotics covering ESBL-producing pathogens to increase the appropriateness of empirical treatment and then narrowing treatment based on culture results appears a better and life-saving choice.

The protective effects of intratympanic dexamethasone and vitamin E on cisplatin-induced ototoxicity are demonstrated in rats.

Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Dexamethasone and vitamin E are two slow-acting free radical cleaners, and they have been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E and dexamethasone as an otoprotectant intratympanically. Prospective, randomized controlled trial in the rat model. Wistar rats were sedated using 50 mg/kg intraperitoneal ketamine and 7.5 mg/kg xylazine. Baseline auditory brainstem response (ABR) testing was performed in response to clicks and 4.8-, 12-, 16-kHz tone bursts. After auditory thresholds were determined, the animals received intraperitoneal drug administration according to one of the four groups. The rat groups received (group I) % 09 NaCl solution intratympanically (IT), (group II) cisplatin (20 mg/kg) only intraperitoneally (IP), (group III) dexamethasone (0.1-0.3 ml) IT and (group IV) vitamin E solution (0.1-0.3 ml) IT followed after 30 min by 20 mg/kg cisplatin. After the 3-day follow-up, ABR testing was performed and threshold changes were recorded. Group II animals showed marked hearing loss with average threshold shifts of 39.7 ± 1.4 dB for clicks, 7.3 ± 2.6 dB at 4 kHz, 8.4 ± 1.6 dB at 8 kHz, 71.1 ± 4.2 dB at 12 kHz and 71.9 ± 5.9 dB at 16 kHz. No significant loss was observed in group III with shifts of 1.60 ± 1.3 dB, 4.75 ± 2.4 dB, 8.7 ± 3.4 dB, and 4.3 ± 2.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. And similar findings were observed in group IV with shifts of 3.3 ± 1.4 dB, 7.2 ± 2.1 dB, 10.8 ± 2 dB, and 13.3 ± 3.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. Significant protection was seen in group III and IV animals compared with group II animals. There is no side effect in IT administration of vitamin E and dexamethasone for hearing functions and two of them appear to have a easier, safer, usable protective effect against cisplatin ototoxicity.

Rosai-Dorfman disease: sinus histiocytosis with massive lymphadenopathy.

A 25-year-old man presented with a 3 month history of a painless mass on the right side of his neck. Physical examination revealed a smooth surfaced, bilobed, 4×3 cm, semimobile mass at the right and 3×2 cm at the left jugulodigastric region. Endoscopic examination of the patient showed a granular tumour in both nasal cavities. After biopsies were taken from the mass from the nasal cavity, a diagnosis of Rosai-Dorfman disease was made. A conservative approach was taken to treatment and after the 6 month follow-up period, the patient was in a stable condition.