Antimicrobial-resistant (AMR) bacterial infections, including those caused by Elizabethkingia anophelis (EA), have emerged as a clinical crisis worldwide. With the increased reports of outbreak and its extensive-antibiotic resistant isolates, the treatment of diseases is challenging. Outer membrane vesicles (OMVs) are purposely secreted by Gram-negative bacteria and contain materials derived from their parent bacterium. OMVs specialize and tailor their functions by carrying different components to challenging environments and communicate with other microorganisms or hosts.

Carbapenem resistant Acinetobacter baumannii (CRAb) is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients, due to limited alternative treatment options. Nine international clonal (IC) lineages have been identified in many countries worldwide, however data still lacks from some parts of the world, particularly in Africa. We hereby present the molecular epidemiology of MDR A. baumannii from four hospitals in Khartoum, Sudan, collected from 2017-2018. Forty-two isolates were whole-genome sequenced, and subsequent molecular epidemiology was determined by core genome MLST (cgMLST), and their resistomes identified. All isolates had an array of diverse antibiotic resistance mechanisms conferring resistance to multiple classes of antibiotics. We found a predominance (88%) of IC2 (with the intrinsic OXA-66 and acquired OXA-23), and some with NDM-1. IC2 isolates were sub-divided into 4 STs separated by 5 to 431 allelic differences, and with evidence of seven transmission clusters. Isolates belonging to IC1, IC5 and IC9 were also identified. These data illustrate that MDR IC2 A. baumannii are widely distributed in Khartoum hospitals and are in possession of multiple antibiotic resistance determinants.

The requirement for a prolonged antibiotic treatment is one of the reasons that limits the global eradication of tuberculosis (TB), mostly due to the mycobacterial tolerance towards antibiotics. Therefore, understanding the factors that are responsible for the drug tolerance of the bacilli is essential in devising efficient treatment strategies and shortening TB chemotherapy and also to prevent the emergence of drug resistance. However, lack of in vitro methods to study the extended time-kill kinetic assays significantly limits our understanding of antibiotic tolerance in M. tuberculosis. The conventional in vitro time-kill kinetic approach with one time antibiotic addition is often associated with the reduction in the effective concentration of the drug in the medium over the period of long incubation. Using a robotic liquid handler controlled Transwell-Tolerance-Resistance (TTR) system, we exposed M. tuberculosis to a steady state antibiotic concentration over a period of 30 days. Our method is a simplified version of the hollow fiber model, wherein each transwell represents an independent culture. The TTR system in 24-well plate format enables us to perform hollow fiber type experiments with hundreds of parallel cultures at different conditions and drug concentrations. This innovation also enables us to perform statistical analyses that are not possible with hollow fiber systems. We find that a steady state rifampicin exposure using TTR system efficiently eliminate drug tolerant forms and prevented emergence of drug resistance at high concentrations compared to the conventional one time treatment. By combining the TTR system with extrachromosomal barcoding, we were able to trace the rifampicin tolerant clones in the population.

In this paper, we deciphered the core resistome disseminating from hospital wastewater to the aquatic environment by characterising the resistome, plasmidome, mobilome and virulome using metagenomic analysis. This study also elucidated different environmental resistome risks using shotgun-metagenomic assembly. The results showed that clinically relevant taxa were found in assessed matrices (Salmonella spp., Acinetobacter spp, Escherichia-Shigella spp., Pseudomonas spp., Staphylococcus spp. and Vibrio spp.). For the plasmidome, we found 249 core plasmidome sequences that were shared among all assessed matrices. The core mobilome of 2 424 mobile genetic elements shared among all assessed matrices was found. Regarding the virulome, we found 148 core virulence factors shared among all assessed samples, and the core virulome content was consistently shared across the most abundant bacterial genera. Although influent of wastewater showed considerable higher relative bacterial abundance (P = 0.008), hospital wastewater showed significant higher environmental resistome risk scores against all other assessed matrices, with an average of 46.34% (P = 0.001). These results suggest hospital wastewater, effluent and sewage sludge should be subjected to stringent mitigating measures to minimise such dissemination.

The purpose of this work was to evaluate flies as mechanical vectors for the spread of Gram negative bacteria resistant to antibiotics. For this, homemade traps with various types of baits were placed to catch flies in different houses both in Cumaná and Carúpano, Sucre state, during the months of February to May 2015. The most attractive bait was fish entrails in both cities. The flies isolated in Cumaná were Chrysomya albiceps, Lucilia cuprina, Sarcophaga sp1 and Musca domestica. In Carúpano were isolated the same of Cumaná, but also Chrysomya rufifacies, Lucilia sericata, Calliphora vicina and Sarcophaga sp2. The Gram negative bacteria carried by the flies were Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa. Some enterobacteria strains were resistant to betalactams by betalactamases production (BLEE, carbapenemases and AmpC), decrease susceptibility to fluoroquinolones and high level resistance to cloramphenicol. We did serino-carbapenemases detection by microbiologic methods, and we saw that Hodge modified test was negative for all strains tested. By antibiotipification we saw low clonality of strains of E. coli isolated from flies. In conclusion, mayority of enterobacteria strains have bacterial resistance mechanisms to all antibiotics of human use (betalactams, fenicols and quinolones), making it impossible to use in case of serious infections. P. aeruginosa strains have resistance to all antibiotics tested.

Every medication has intended effect(s) or indication(s), and side effects or adverse drug reactions. Such side effects may or may not happen even if the dose was within acceptable range. For instance, vancomycin is known to be a powerful antibiotic to eradicate Methicillin Resistant Staphylococcus Aureus (MRSA) when used appropriately. However, it could potentially cause acute kidney injury since it is dependent on individual's actual body weight and kidney function to be cleared out of the body system, unless otherwise the dose regimen was tailored properly with timely monitoring of the serum trough level. Furthermore, every individual react to each medication differently; some are prone to unwanted reactions compared to others. That in part is attributed to the varying physiological status which affects pharmacokinetics and pharmacodynamics of the drug. Not to mention the effect of genetic polymorphisms, which are known to influence outcomes with certain medications. Hence, it is tremendously important to establish suitable dose regimen and maintain safe and effective serum concentrations of such medications on a timely manner in order to optimize pharmacological efficacy and eliminate, or at least minimize, potential harm. The objective of this presentation is discuss the therapeutic updates as well as best practices of Vancomycin therapeutic drug monitoring both for adults and pediatrics.

The lethal game between microbes and vertebrates has been ongoing for hundreds of millions of years. Both have the ability to mutate their offensive and defensive weapons. We certainly see the microbes doing this on a much shorter time scale. Thus, antibiotic resistance has become an issue in less than 150 years.
Animals, including vertebrates developed a class of defensive weapons such as the cationic membrane disruptive polypeptides, including the human beta-defensins (hBDs) and the cathelicidin, LL-37. These antimicrobial peptides (AMPs) have become part of our innate immune system and are produced by activating toll-like receptors (TLRs) on keratinocytes, epithelial cells, and immune cells. In other words, all our tubes and surfaces are capable of defending themselves.
These AMPs attack a fundamental part of bacteria and enveloped viruses, the cell or plasma membrane, a structure mammalian cells possess abilities to repair. In contrast, this repair ability is not shared or is far less developed by our less complicated adversaries. Indeed, the structure cannot be altered; however, enzymes developed to attack AMPs are certainly one strategy being utilized.
Synthetic versions of these bioactive membrane molecules (cationic lipo-oligopeptides or CLOPs) have been known and well studied for the last 45 years. What has not been well studied and we are reporting on in this forum is the use of CLOPs in nano-emulsion formulation to directly stimulate TLRs, thus up-regulating AMPs. These up-regulated AMPs now can directly kill microbials and enveloped viruses independent of the antibiotics present. The ability of TLR agonists to aid in the fight against resistant strains is a promising approach for pre-clinical research.

Introduction: Tigecycline is a unique class of semi-synthetic glycylcyclines developed to treat infections caused by multidrug-resistant Klebsiella pneumoniae. In the past decades, eight tigecycline-resistant Acinetobacter baumannii isolates have been identified in Tehran and no Klebsiella pneumoniae has been reported.
Methodology: To elucidate the mechanism of K. pneumoniae efflux pump-mediated resistance, the expression of efflux pump genes (oqxA, oqxB, acrA, acrB, tolC) and regulators (acrR, ramA, marA, soxS, rarA, rob) was investigated by real-time RT-PCR. Multilocus sequence typing (MLST) of tigecycline-resistant strains was also performed.
Results: Compared to the tigecycline sensitive strain K32 (negative control), all resistant strains showed higher expression levels of efflux genes and regulatory factors. Three tigecycline-resistant strains (K53, K67, K79) showed higher levels of rarA expression (38.1-fold, 41-fold and 24-fold, respectively) and oqxB pump gene (48.2-fold, 60-fold and 58-fold, respectively). The increased expression of acrB was associated with the expression of ramA. However, to the best of our knowledge, studies on the mechanisms of resistance of K. pneumoniae strains to tigecycline are limited, especially in developing countries such as Iran.
Conclusions: In the present study, we found that both AcrAB-TolC and OqxAB efflux pumps may play an important role in tigecycline resistance in K. pneumoniae isolates. Finally, the emergence of ST11 molecular type of resistant isolates should be monitored in hospitals to identify factors leading to tigecycline resistance.
Keywords: Klebsiella pneumoniae; MLST; RT-PCR; Tigecycline; efflux pump genes; real-time PCR.

Drugs have been used for the treatment of infectious diseases since the 17th century. Antimicrobial drugs act in one of several ways: by selective toxicity, by inhibition of cell membrane synthesis and function, by inhibition of protein synthesis, or by inhibition of nucleic acid synthesis. Antibiotics are actually those antimicrobial substances which are active against bacteria for fighting bacterial infections, either by killing or inhibiting the growth of bacteria. Antibiotics are generally safe but they have many risks associated with their use like having hypersensitivity adverse reactions, anaphylactic shocks, allergic reactions etc. An ideal antimicrobial agent exhibits selective toxicity. Inhibition of cell wall synthesis, cell membrane functions, protein synthesis, nucleic acid synthesis and antimetabolite activity are the five basic mechanisms of antibiotic action against bacterial cells. Antibiotics can be divided into two classes based on their mechanism of action. Bactericidal antibiotics kill bacteria and bacteriostatic antibiotics inhibit their growth or reproduction. A large number of antibiotic types have been discovered in these previous years among which Penicillins,Tetracyclines, Cephalosporins, Quinolones, Lincomycins, Macrolides, Sulfonamides and so many are important to treat bacterial infections.

Antimicrobial resistance (AMR) has been detected in all parts of the world. It is currently one of the greatest challenges to global public health. (WHO 2014).It has been estimated   that failure to address the problem globally could result in 10 million deaths by 2050. ¹

Two key areas which are essential for prevention and control of MDROs in Health care facilities are: (i) Effective implementation of an antibiotic stewardship programme to prevent the emergence of resistant microorganisms

                      (ii) Implementation of infection control measures.²

Inappropriate and indiscriminate use of antibiotics exerts selective pressure and lead to the emergence of multidrug-resistant organisms. Narrow spectrum antibiotics should be used as a first line therapy based on local antibiotic susceptibility data. ³

Infection prevention and control guidelines must be developed for prevention and control of MDROs. It should include risk assessment and triage so that known or suspected cases are promptly identified, segregated and isolated without dely. Standard precautions like hand hygiene is one of the most important interventions to prevent cross infections and this must be rigorously enforced as per WHO 5 moments of hand hygiene⁴. Surveillance of MDROs must be done to monitor the incidence and epidemiologic trends of various MDROs over time.⁵