Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes

Funder: Rhodes Scholarships; doi: http://dx.doi.org/10.13039/501100000697Funder: Bill and Melinda Gates Foundation; doi: http://dx.doi.org/10.13039/100000865Abstract: Background: India is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors. Blood culture surveillance was conducted at St. John’s Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease. Results: Among the 113 cases of blood culture-confirmed enteric fever, young adults (16–30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children (p = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate S. Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters. Conclusions: Amidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies

BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias

Pseudotumor cerebri following traumatic brain injury in a 29-year-old man

We describe a case of pseudotumor cerebri in a young man developing 4 years post-traumatic brain injury (TBI). A 29-year-old man was admitted after sustaining a fall with headache, and no clinical deficits were noted on examination. CT brain demonstrated an extradural hematoma. This was successfully evacuated after his symptomatic worsening. Following this, he developed bone flap infection and had the infected bone flap removed. He developed chronic mild-to-moderate headache following these procedures, which failed to respond to medical treatment. Pseudotumor cerebri was diagnosed. A lumboperitoneal (LP) shunt, ventriculo-peritoneal (VP) shunt, and bitemporal craniectomy were performed as a part of management at different stages. Post-TBI patients may present with chronic headache and in such circumstances, a possibility of pseudotumor cerebri must be considered. Investigations should include neuroimaging in the form of MRI/MRV and fundoscopy to look for papilledema. Management in the form of CSF flow diversion techniques (VP and LP shunt) with medical management results in good clinical outcome

Moraxella catarrhalis: A Cause of Concern with Emerging Resistance and Presence of BRO Beta-Lactamase Gene—Report from a Tertiary Care Hospital in South India

Background. Found as a commensal in the upper respiratory tract, Gram-negative diplococcus Moraxella catarrhalis did not hold much importance as an infectious agent for long. The emergence of the first antibiotic-resistant strain of M. catarrhalis was noted in 1977 in Sweden. This has gradually spread worldwide over the years to more than 95% of the strains showing resistance to penicillin now. Penicillin resistance is mediated by the production of beta-lactamases encoded by bro-1 and bro-2 genes that code for beta-lactamases BRO-1 and BRO-2, respectively. The purpose of this study was to explore the trends of antibiotic resistance, the presence of bro genes, and clinical correlation of these findings with the rise in M. catarrhalis infections worldwide. Methods. Strains of M. catarrhalis were isolated from the respiratory samples submitted to the microbiology laboratory. Preliminary identification was done using standard microbiological techniques, and antibiotic sensitivity was determined by minimum inhibitory concentration assessed using the E-test. Further, the genes associated with the development of resistance to penicillin (beta-lactamase enzyme) were detected using polymerase chain reaction technique. Results. Fourteen strains of M. catarrhalis were isolated during the study period. Majority of the strains were isolated from patients between 40 and 60 years of age and from males. Seasonality was observed with most strains being isolated during the winter season. The most important predisposing factors identified were advanced age with a history of smoking and chronic obstructive pulmonary disease. The antibiotic susceptibility pattern showed resistance to most antibiotics commonly used for the treatment of respiratory tract infections. Finally, all the strains were beta-lactamase producers, confirmed by the detection of bro-1 beta-lactamase gene in them. Conclusion. The increase in antibiotic resistance and beta-lactamase production in M. catarrhalis is a cause of concern. The emerging resistance pattern emphasises the need for an appropriate antibiotic stewardship program in clinical practice. Importance should be given to the monitoring of the trends of antibiotic susceptibility and their usage to prevent the emergence of outbreaks with resistant strains and treatment failures

Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes.

Background: India is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors.Blood culture surveillance was conducted at St. John's Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease. Results: Among the 113 cases of blood culture-confirmed enteric fever, young adults (16-30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children (p = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate S. Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters. Conclusions: Amidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies