Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria.

We discovered azaindole-based compounds with weak innate activity that exhibit substantial potentiation of antibacterial activities of different antibiotics, viz., rifampicin, erythromycin, solithromycin, and novobiocin in Gram-negative bacteria. In the presence of the azaindole derivatives, these antibiotics exhibited submicromolar minimum inhibitory concentrations (MICs) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The fold improvements in MIC of these antibiotics that were otherwise weak or inactive on their own against these bacteria were also observed against drug-resistant clinical isolates. Our studies indicate that this selective potentiation is probably through destabilization of the outer membrane's integrity, known to be regulated by the lipopolysaccharides (LPS). Thus, the azaindole based compounds described here open opportunities for those antibiotics that are otherwise ineffective due to LPS mediated entry barriers in Gram-negative bacteria.

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.

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 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. METHODS: Strains 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. RESULTS: Fourteen strains 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. 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.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.

In situ free-floating craniectomy: an unusual cause of chronic post-traumatic cephalalgia.

We describe a case of post-traumatic cephalalgia in a 54-year-old man with chronic right parieto-occipital headache 3 years posthead injury. At the initial presentation, his Glasgow Coma Scale (GCS) was 13/15 and CT brain revealed an acute subdural haematoma with fronto-temporal contusions. After 24 h his GCS dropped to 8/15 and subsequently he underwent a right-sided craniotomy and evacuation of the subdural haematoma and contusionectomy and intracranial pressure monitoring. To manage the cerebral oedema, the cranial bone flap was left in situ free-floating and was managed in an intensive care setting. He made good clinical recovery and 3 months postoperatively he complained of right-sided headache not relieved with medication and occipital nerve block. Three years later he underwent an exploration of the previous craniotomy scalp wound and the free-floating bone flap under the scalp was immobilised. The headache completely resolved following the procedure and is currently asymptomatic.

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 outcomes.