Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic nosocomial pathogen associated with high morbidity and mortality rates. Combination of antibiotics has been found to combat multi-drug resistant or extensively drug resistance P. aeruginosa. In this study we investigate the in vitro and in vivo effect of amikacin and imipenem combination against resistant P. aeruginosa. The checkerboard technique and time-killing curve have been performed for in vitro studies showed synergistic effect for combination. A peritonitis mouse model has been used for evaluation of the therapeutic efficacy of this combination which confirmed this synergistic effect. The in vitro and in vivo techniques showed synergistic interaction between tested drugs with fractional inhibitory concentration indices (FICIs) of ≤0.5. Conventional PCR and quantitative real-time PCR techniques were used in molecular detection of bla IMP and aac(6′)-Ib as 35.5% and 42.2% of P. aeruginosa harbored bla IMP and aac(6′)-Ib respectively. Drug combination viewed statistically significant reduction in bacterial counts (p value < 0.5). The lowest bla IMP and aac(6′)-Ib expression was observed after treatment with 0.25 MIC of imipenem + 0.5 MIC of amikacin. Morphological changes in P. aeruginosa isolates were detected by scanning electron microscope (SEM) showing cell shrinkage and disruption in the outer membrane of P. aeruginosa that were more prominent with combination therapy than with monotherapy.

Dissecting Host-Pathogen Interactions in TB Using Systems-Based Omic Approaches

Tuberculosis (TB) is a devastating infectious disease that kills over a million people every year. There is an increasing burden of multi drug resistance (MDR) and extensively drug resistance (XDR) TB. New and improved therapies are urgently needed to overcome the limitations of current treatment. The causative agent, Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens that can manipulate host cell environment for adaptation, evading immune defences, virulence, and pathogenesis of TB infection. Host-pathogen interaction is important to establish infection and it involves a complex set of processes. Metabolic cross talk between the host and pathogen is a facet of TB infection and has been an important topic of research where there is growing interest in developing therapies and drugs that target these interactions and metabolism of the pathogen in the host. Mtb scavenges multiple nutrient sources from the host and has adapted its metabolism to survive in the intracellular niche. Advancements in systems-based omic technologies have been successful to unravel host-pathogen interactions in TB. In this review we discuss the application and usefulness of omics in TB research that provides promising interventions for developing anti-TB therapies.

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9%) were identified as hvKP and 78.6% (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85%) followed by K1 (35.71%). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9%), 5 (35.7%) and 1 (7.1%), respectively. ESBL production was found in 85.7% of hvKP isolates and most of them carried bla TEM gene (78.6%) and 6 isolates (42.9%) were CR-hvKP. Among hvKP isolates, 1 (7.1%), 2 (14.3%), 3 (21.4%), 8 (28.6%), and 11 (78.6%) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance.

Determination of drug resistance of Mycobacterium tuberculosis in the operating material

Currently, with the improvement of epidemic indicators for tuberculosis, the number of patients with drug-resistant forms of tuberculosis is increasing, which complicates and prolongs the treatment of such patients. The aim of the work is to study the drug resistance of Mycobacterium tuberculosis obtained from surgical material. Materials and methods: the study included 74 patients with medical and diagnostic operations on the chest organs. All patients were examined by standard methods: sputum and BAL microscopy with bronchoscopy (during the procedure), molecular genetic methods, culture on dense and liquid nutrient media. The diagnosis of tuberculosis was confirmed morphologically in all patients by histological examination of surgical material. When analyzing the results of drug resistance, it was found that among the newly identified patients, more than half (59.3%) had multiple (44.6%) p<0.005 and extensively drug resistance (14.7%) p= 0.003. At the same time, 74.5% (n= 35/47) of patients had no MBT in sputum before surgery. The frequency of development of drug resistance to first-and reserve-line antibacterial drugs, the structure of drug resistance depending on the group of dispensary registration is presented. A comparative analysis of drug sensitivity testing of MBT isolated from sputum before surgery and from surgical material was performed. The results of the study showed a high percentage of MBT drug resistance obtained in the operating material in patients with negative MBT tests. More than half of the patients who did not receive antibacterial therapy before surgery have multi drug resistance and extensively drug resistance, which suggests a high regional primary drug resistance of Mycobacterium tuberculosis.

Extra-Pulmonary TB

Tuberculosis is considered a fatal respiratory disease commonly seen in developing countries. This chapter includes the global scenario of TB patients and brief description of TB history, its pathogenesis, types, diagnosis tests, emergence of MDR (multi drug resistance) and XDR (extensively drug resistance). The traditional chemotherapy of TB includes first and second line drug therapy. These lines of therapies face many difficulties such as low solubility, low bioavailability, and stability issues. Therefore, some new drugs were introduced in the market that showed effective results to the patients. Nanoparticulate drug delivery gained much focus in recent years due to its advantages and ideal characteristics. Numerous nanoparticles, liposomal formulations, and polymeric micelles were reported by the researchers with significant and considerable results. Inhalable formulations were also prepared by scientists that showed effective and remarkable anti-tuberculosis action on TB patients. Many efforts are awaited to completely eradicate TB from the planet.

Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

Novel Vaccine Candidates against Tuberculosis

Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs’ efficacy is limited by a series of problems such as Multi- Drug Resistance (MDR) and Extensively-Drug Resistance (XDR). Meanwhile, the only licensed vaccine BCG (Bacillus Calmette-Guérin) existing for over 90 years is not effective enough. Consequently, it is essential to develop novel vaccines for TB prevention and immunotherapy. This paper provides an overall review of the TB prevalence, immune system response against TB and recent progress of TB vaccine research and development. Several vaccines in clinical trials are described as well as LAM-based candidates.

Recent Advancement in Predicting Subcellular Localization of Mycobacterial Protein with Machine Learning Methods

Mycobacterium tuberculosis (MTB) can cause the terrible tuberculosis (TB), which is reported as one of the most dreadful epidemics. Although many biochemical molecular drugs have been developed to cope with this disease, the drug resistance—especially the multidrug-resistant (MDR) and extensively drug-resistance (XDR)—poses a huge threat to the treatment. However, traditional biochemical experimental method to tackle TB is time-consuming and costly. Benefited by the appearance of the enormous genomic and proteomic sequence data, TB can be treated via sequence-based biological computational approach-bioinformatics. Studies on predicting subcellular localization of mycobacterial protein (MBP) with high precision and efficiency may help figure out the biological function of these proteins and then provide useful insights for protein function annotation as well as drug design. In this review, we reported the progress that has been made in computational prediction of subcellular localization of MBP including the following aspects: 1) Construction of benchmark datasets. 2) Methods of feature extraction. 3) Techniques of feature selection. 4) Application of several published prediction algorithms. 5) The published results. 6) The further study on prediction of subcellular localization of MBP.