Staphylococcus aureus is an increasing problem in clinical practice because of reduced susceptibility to available antibiotics. The objective of the study was to determine the frequency of Methicillin-resistant S.aureus (MRSA) in Peshawar, Pakistan. Clinical isolates of S. aureus were subjected to determination of antibiotic resistance, MICs and inducible clindamycin resistance (ICR). Out of total 280 S. aureus isolates, the frequency of MRSA was 36.1 % (n = 101). MRSA infection was found higher among the age group 50–59 years (60.71 %, OR 3.09), followed by 20–29 years (47.5 %, OR 1.74). Frequency of MRSA in female and male was 39.8 and 34 % respectively. MRSA was more frequent in blood specimens (48.7 %, OR 2.14). The frequency of community and hospital acquired MRSA was 42 and 34.8 % respectively. MRSA showed high resistance (100 %) to penicillin and cefoxitin followed by erythromycin (99 %). While MRSA exhibited 100 % susceptibility to vancomycin and linezolid. We have also found 7 vancomycin intermediate sensitive S. aureus (VISA) isolates. ICR was observed in 15.84 % (n = 16) of MRSA isolates. It is concluded that MRSA is potential threat to public health in Peshawar. Vancomycin and linezolid could be prescribed as a drug of choice in treating MRSA associated infections. In addition, ICR should be routinely checked to avoid clindamycin treatment failure.
Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.
Chimeric antigen receptor (CAR) T-cells are redirected T-cells that can recognize cancer antigens in a major histocompatibility complex (MHC)-independent fashion. A typical CAR is comprised of two main functional domains: an extracellular antigen recognition domain, called a single-chain variable fragment (scFv), and an intracellular signaling domain. Based on the number of intracellular signaling molecules, CARs are categorized into four generations. CAR T-cell therapy has become a promising treatment for hematologic malignancies. However, results of its clinical trials on solid tumors have not been encouraging. Here, we described the structure of CARs and summarized the clinical trials of CD19-targeted CAR T-cells. The side effects, safety management, challenges, and future prospects of CAR T-cells for the treatment of cancer, particularly for solid tumors, were also discussed.
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