Inapropriate use of antibiotics effective against gram positive microorganisms despite restrictive antibiotic policies in ICUs: a prospective observational study.

BACKGROUND: Gram-positive spectrum antibiotics such as vancomycin, teicoplanin, daptomycin, and linezolid are frequently used in empirical treatment combinations in critically ill patients. Such inappropriate and unnecessary widespread use, leads to sub-optimal utilisation. However they are covered by the antibiotics restriction programme. This prospective observational study, evaluates gram-positive anti-bacterial utilisations in intensive care units (ICUs) with various evaluation criteria, to determine the frequency of inappropriate usage and the intervention targets required to ensure optimum use. METHODS: This clinical study was conducted prospectively between 01.10.2018 and 01.10.2019 in the medical and surgical ICUs of Gazi University Faculty of Medicine Hospital, Turkey. The total bed capacity was 55. Patients older than 18 years and who were prescribed gram-positive spectrum antibiotics (vancomycin, teicoplanin, linezolid, and daptomycin) were included. Patients under this age or immunosuppressed patients (neutropenic,- HIV-infected patients with hematologic or solid organ malignancies) were not included in the study. During the study period, 200 treatments were evaluated in 169 patients. The demographic and clinical features of the patients were recorded. Besides observations by the clinical staff, the treatments were recorded and evaluated by two infectious diseases specialists and two clinical pharmacists at 24-h intervals from the first day to the last day of treatment. SPSS software for Windows, (version 17, IBM, Armonk, NY) was used to analyse the data. Categorical variables were presented as number and percentage, and non-categorical variables were presented as mean ± standard deviation. RESULTS: It was found that inappropriate gram-positive antibiotic use in ICUs was as high as 83% in terms of non-compliance with the selected quality parameters. Multivariate analysis was performed to evaluate the factors associated with inappropriate antibiotic use, increased creatinine levels were found to increase the risk of such use. CONCLUSIONS: In spite of the restricted antibiotics programme, inappropriate antibiotic use in ICUs is quite common. Thus, it is necessary to establish local guidelines in collaboration with different disciplines for the determination and follow-up of de-escalation of such use and optimal treatment doses.

Meropenem, rifampicin and gentamicin combination therapy in a patient with complicated urinary tract infection caused by extreme drug-resistant P. aeruginosa.

In this article, we report a case of a 25-year-old male patient who was under follow-up for nephrolithiasis and repeated urological interventions. His last operation was carried out 9 months ago for insertion of a double-J catheter. Pseudomonas aeruginosa, which is susceptible to only colistin treatment, was detected in the urine culture. Before the removal of the double-J catheter, colistin and ceftazidime antibiotics were started to prevent the risk of bloodstream infection. However, the treatment was stopped urgently due to signs of nephrotoxicity. His treatment was restarted with colistin 300 mg once as the initial loading dose, followed by 150 mg/day. However, this time, colistin neurotoxicity has developed and the treatment was again stopped. Meropenem 6 g/day, gentamicin 2 mg/kg and rifampicin 300 mg were prescribed. Negative urine culture was achieved on the fifth day of treatment.

New Therapeutic Approaches in Cystic Fibrosis.

Cystic fibrosis (CF) is a hereditary, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator. CF is mainly characterized by pulmonary dysfunction as a result of deterioration in the mucociliary clearance and anion transport of airways. Mortality is mostly caused by bronchiectasis, bronchiole obstruction, and progressive respiratory dysfunction in the early years of life. Over the last decade, new therapeutic strategies rather than symptomatic treatment have been proposed, such as the small molecule approach, ion channel therapy, and pulmonary gene therapy. Due to considerable progress in the treatment options, CF has become an adult disease rather than a pediatric disease in recent years. Pulmonary gene therapy has gained special attention due to its mutation type independent aspect, therefore being applicable to all CF patients. On the other hand, the major obstacle for CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity. The advancement of 3D culture systems has made it possible to extrapolate the disease modeling and individual drug response in vitro by producing mini adult organs called "organoids" obtained from rectal cell biopsies. In this review, we summarize the advances in the novel therapeutic approaches, clinical interventions, and precision medicine concept for CF.