RESUMO
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.
RESUMO
BACKGROUND: Plant-derived products or extracts are widely used in folk/traditional medicine to treat several infections, ailments, or disorders. A well-known medicinal herb, Myrtus communis is an evergreen fragrant plant native to the Mediterranean region that has been used for ages in traditional medicine around the world. MATERIALS AND METHODS: The microplate alamarBlue assay and the well diffusion method were used to evaluate the zone of inhibition and MIC, respectively. The double-disc diffusion method was used to investigate the synergy between antibiotics and the extract. The crystal violet method was used to investigate biofilm development. The SulphoRhodamine-B assay and DNA flow cytometry were used to investigate the proliferation and subsequent distribution of cells among different phases of the cell cycle. The apoptotic and necrotic phases of the cancer cells were examined using flow cytometry in conjunction with Annexin V-FITC/PI labeling. Using the IBM SPSS statistical program, a one-way ANOVA with Tukey's post hoc test was employed for statistical analysis. RESULTS: The ethanolic leaf extract of M. communis showed a strong growth inhibition effect (zone of inhibition: 20.3 ± 1.1-26.3 ± 2.5 mm, MIC: 4.88-312.5 µg/mL, and MBC: 39.07-1250 µg/mL) against several rapidly growing and slow-growing mycobacterial strains in a dose-dependent manner. Damage to the cell wall of bacterial cells was determined to be the cause of the antimycobacterial action. The extract inhibited biofilm formation (MBIC of 9.7 µg/mL) and eradicated already-formed mature and ultra-mature biofilms of M. smegmatis, with MBEC values of 78 µg/mL and 156 µg/mL, respectively. Additionally, the extract exhibited potent anticancer effects against diverse cancer cell lines of the breast (MCF-7), liver (HepG2), cervix (HeLa), and colon (HCT116) (IC50 for HCT116: 83 ± 2.5, HepG2: 53.3 ± 0.6, MCF-7: 41.5 ± 0.6, and HeLa: 33.3 ± 3.6) by apoptosis after arresting the cells in the G1 phase of the cell cycle. CONCLUSIONS: These results suggest that M. communis leaf extract is a potential source of secondary metabolites that could be further developed as potential anticancer and antimycobacterial agents to treat diverse types of cancers and mycobacterial infections.