The sessions discuss various abstract presentations on preventing infectious disease, antimicrobial resistance in Sri Lanka, efficacy of cefiderocol, use of antibiotics in poultry, prevalence of resistant enterococcus species, linezolid and vancomycin resistance, S. typhi resistance, pre-clinical development of human monoclonal antibodies, epidemiology of S. aureus in India and the use of intravenous doxycycline or azithromycin in scrub typhus management.

A study conducted in Sri Lanka has shown that about 40% of the isolates obtained from urinary tract infection patients are extended spectrum beta lactamase (ESBL) Enterobacteriaceae. While the data on humans is sufficient to understand the burden, the data on livestock, wildlife and environment is scarce. A study conducted on the fecal samples of livestock and wildlife in a small area in Sri Lanka revealed E. coli colonization. When this bacteria was tested for resistance, the highest resistance in livestock was observed for tetracycline (52%) followed by ampicillin (39%) and nalidixic acid (37%). The highest resistance in wildlife was seen for streptomycin (45%) followed by ampicillin (12%) and trimethoprim sulfamethoxazole (6.9%). With respect to the prevalence of multidrug resistant E.coli, 32% were from livestock, 7% from wildlife, 12% from soil, and 31% were from water. These elicit the need for a judicial use of antimicrobials.

Cefiderocol, a siderophore cephalosporin, has a novel mode of entry into bacteria, it has more stability against carbapenems and has potent activities against all carbapenem-resistant and non-fermentative gram-negative bacilli. It has an action against all enzymes such as carbapenemase as well as the efflux and pseudomonas enzymes. A recent Indian study (2021) has demonstrated prevalence of carbapenem-resistant gram-negative bacteria to be > 50% in hospital settings. In patients admitted with sepsis, pneumonia or urinary tract infection infected with carbapenem resistant gram-negative organism, among all E. coli strains, 60% was sensitive, 100% K. pneumoniae isolates were sensitive, for Pseudomonas 43% were sensitive and for Acinetobacter, 33.3% were sensitive. The susceptibility of Cefiderocol in this sample was 60%. Further studies are needed to study the susceptibility of Cefiderocol in the Indian scenario.

The excessive use of livestock antibiotics contributes to the rapid decimation of AMR globally. In Bangladesh, antibiotics are used in commercial poultry production to treat disease and as growth promoters with maximum use found in broiler farms. An ethnographic study which conducted interviews with farmers, veterinarians, food marketing officers and farmers respondents revealed that these groups found antibiotics to be a powerful medicine to treat poultry disease. The pharmaceutical representatives played an important role interpreting the role of antibiotics in poultry farming. They motivated the veterinarians, dealers and farmers to prescribe, dispense and use antibiotics through their innovative marketing system. These findings will help to develop an effective policy for the proper use of antibiotics in animals and how to direct the right messages on AMR to raise awareness among the stakeholders. 

 

A study conducted in Delhi, India on 961 enterococci isolates from urine, blood and placenta showed that the prevalence of linezolid resistance enterococci in urine, blood and pus samples 13%, 25% and 13% respectively.  The prevalence of vancomycin resistance in urine, blood and pus samples was 24%, 44% and 18% respectively. The resistance for both was highest in the blood isolates. Prolonged exposure to antibiotics is the most striking factor for AMR. 

Extensively drug-resistant (XDR) XDR Salmonella is resistant to three first line drugs as well as fluoroquinolones and 3rd generation cephalosporins and they are only treated with carbapenems and azithromycin. A whole genome sequencing from the XDR salmonella type for genotyping, antimicrobial gene prediction and phylogenetic analysis was conducted in Pakistan. In the samples, 27 isolates of S. typhi were isolated; all isolates were resistant to standard treatment including ceftriaxone. All the XDR isolates differed by 6 single nucleotide polymorphism (SNPs) from the MDR S. typhi clade suggesting that it is a clonal pathogen. 

Systemic fungal infections, which is an area of huge unmet medical need and pathogenic fungi can cause life threatening infections in immunocompromised patients like those undergoing chemotherapy, organ transplant or HIV positive individuals. An antifungal monoclonal antibody detection programme was conducted using the phage display technique to develop monoclononal antibodies. These antibodies were characterized by the antigen binding of these antibodies on the Candida cell surface, their cross-reactivity to other pathogenic fungi and their ability to recruit effector cells such as macrophages and neutrophils.  It was found that cell wall proteins are upregulated which is more than two-fold increase in expression in their proteome levels and transcriptome levels. Among these proteins, Utr2 and Pga31 were used for further study. Using these targets, human monoclonal antibodies were created which showed that these antibodies can bind to whole Candida cells and a confirmed target specificity and cell surface binding, These antibodies also had a preferential binding to the hyphae which aid tissue penetration and destruction during infection. When cells were pretreated with these antibodies, there was a significant increase in the involvement by macrophage and there was an increase in the phagocytic index. These successful findings have led to the commercial development of these antibodies presently.

The session discussed the results of a retrospective genomic study on S. aureus which was a part of a larger study with global database. A total of 478 isolates from 38 clinical centres across India were conducted for this retrospective surveillance to find out the resistance pattern and virulence factors. It was found that whole genome sequencing helped to identify 2 new sub-lineages of multi-drug resistant and ST22 isolates. The temporal reconstruction of the spread of ST 22 showed that these new sublineages had originated around 1980 in India. The Indian ST22 clones are very distinct from the Gaza clones and are known to carry a specific set of genes (TSST gene as reported in this study).

Scrub typhus is a mite born zoonotic bacterial infection causing about 1 million cases annually, resulting in 150,000 deaths. More than 1 billion people are at risk in the endemic region called the 'Tsutsugamushi triangle' in Southeast Asia. One third of cases develop the severe form of disease, resulting in multi-organ dysfunction with a mortality as high as 24% despite diagnosis and treatment. Although doxycycline and azithromycin are most common antibiotic treatments, there is a lack of clinical data in the management of scrub typhus. In addition, the availability of the intravenous forms of these drugs is insufficient. There are some small randomized control trials comparing azithromycin and doxycycline in mild scrub typhus. However, these are underpowered. A randomized, double-blind, placebo controlled trial to determine the best intravenous treatment strategy for severe typhus was conducted in India. The trial included including 794 patients >15 years of age with severe typhus. The trial determined the reduction in mortality and improvement of complications as a composite end point across seven centers in India. It was found that combination therapy with doxycycline and azithromycin resulted in lower composite outcome as compared to individual drugs. There were less number of persisting complications on day 7 with combination treatment. This suggested the benefit of combination therapy over monotherapies with doxycycline or azithromycin in the management of scrub typhus.

OP 04 International Society for Infectious Diseases (ISID) Congress 2022, 17th-20th Nov. 2022, Malaysia







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