Antimicrobial Resistance

Klebsiella pneumoniae (K. pneumoniae) pose an emerging threat to public health sector worldwide. They are one of the potent nosocomial pathogens and cause variety of infections including pneumonia, septicaemia, wound infections, urinary tract infections and catheter-associated infections. From the last two decades, these pathogens are becoming more powerful due to the acquisition of resistomes on different types of plasmids and transposons. There are four main mechanisms of antibacterial resistance such as efflux pump, target alteration, membrane permeability and notably enzymes hydrolysis. K. pneumoniae produce different types of enzymes but most importantly extended spectrum-β-lactamase (ESBL), carbapenemase and metallo-β-lactamase (MBL). K. pneumoniae carbapenemases (KPCs) and New Delhi metallo-β-lactamase (NDM) producing isolates displayed resistance not only against the β-lactam drugs (penicillins, cephalosporins and carbapenems) but also to other classes of antibiotics (aminoglycosides and quinolones). Therapeutic options available to treat serious infections caused by these extensively drug-resistant pathogens are limited to colistin, tigecycline and fosfomycin. Hence, combination therapy has also been recommended to treat such bacteria with clinical side effects, therefore, new treatment regime must be required. Moreover, we are relying on conventional diagnostic tools, however, novel techniques must be required for robust identification of multi-drug-resistant bacteria

Innovative Strategies for the Control of Biofilm Formation in Clinical Settings

Biofilm formation in clinical settings is an increasingly important issue particularly due to the emergence of multidrug-resistant strains, as it resulted in increased mortality, which poses a considerable financial burden on healthcare systems. The bacterial biofilms are quite resistant to the routine antimicrobial-based therapies; therefore, the novel strategies are desired in addition to the conventional antibiotics for the effective control of infections caused by biofilm-forming microbes. So far, the approaches being proposed to control the biofilm formation in clinical practice settings include the use of biofilm inhibitors and the use of modified biomaterials for the development of medical devices to thwart the formation of biofilms. In this chapter, we have focused on the latest developments in the anti-biofilm strategies through the interruption of the quorum-sensing system, which is crucial for biofilm formation and have summarized the various classes of antibacterial compounds for the control of biofilm formation. This agrees with the recent approaches suggested by the National Institute of Health (NIH) that advocates the use of combinational therapies based on the conventional methods and complementary treatment to explore the potential utility and safety concerns of the natural products. The studies regarding these emerging strategies could possibly lead to the establishment of better therapeutic alternates compared to conventional treatments

Hurdles in Vaccine Development against Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide and also forms a serious threat for the elderly. Vaccination could significantly relieve the burden of the RSV disease. However, unfortunately there is no licensed vaccine available so far. This is partly due to disastrous outcome of a clinical trial of formalin-inactivated RSV (FI-RSV) in children in 1960s; leading to enhanced respiratory disease upon natural infection. These findings contributed significantly to the delay of RSV vaccine development. Other key obstacles in development of RSV vaccine such as a peak of severe disease at 2–3 months of age, challenging biochemical behavior of key vaccine antigens and dependence on animal models that may not truly reflect human disease processes. These challenges could be overcome through maternal immunization, structure-based engineering of vaccine antigens, the design of a novel platform for safe infant immunization, and the development of improved animal models. Currently, several vaccine candidates are in pre-clinical and clinical trials targeting the diverse age groups; young children or older adults from the infection or can reduce incidence, mortality and morbidity among the RSV infected individuals

Carbapenem Resistance: Mechanisms and Drivers of Global Menace

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace

Emergence of resistance to fluoroquinolones and third-generation cephalosporins in Salmonella Typhi in Lahore, Pakistan

Extensively drug-resistant (XDR) Salmonella Typhi has been reported in Sindh province of Pakistan since 2016. The potential for further spread is of serious concern as remaining treatment options are severely limited. We report the phenotypic and genotypic characterization of 27 XDR S. Typhi isolated from patients attending Jinnah Hospital, Lahore, Pakistan. Isolates were identified by biochemical profiling; antimicrobial susceptibility was determined by a modified Kirby-Bauer method. These findings were confirmed using Illumina whole genome nucleotide sequence data. All sequences were compared to the outbreak strain from Southern Pakistan and typed using the S. Typhi genotyping scheme. All isolates were confirmed by a sequence analysis to harbor an IncY plasmid and the CTX-M-15 ceftriaxone resistance determinant. All isolates were of the same genotypic background as the outbreak strain from Sindh province. We report the first emergence of XDR S. Typhi in Punjab province of Pakistan confirmed by whole genome sequencing