Severe Group A and Group B Streptococcus Diseases at a Pediatric ICU: Are they Still Sensitive to the Penicillins?

BACKGROUND: Group A ß-hemolytic Streptococcus (GAS) and Group B streptococcus (GBS) are two common pathogens that are associated with many diseases in children. Severe infections as a result of these two streptococci are albeit uncommon but associated with high mortality and morbidity, and often necessitate intensive care support. This paper aims to review the mortality and morbidity of severe infection associated with GAS and GBS isolations at a Pediatric Intensive Care Unit (PICU). METHODS: All children admitted to PICU of a teaching hospital between October 2002 and May 2018 with laboratory-proven GAS and GBS isolations were included. RESULTS: There were 19 patients (0.7% PICU admissions) with streptococcal isolations (GAS, n=11 and GBS, n=8). Comparing to GAS, GBS affected infants were younger (median age 0.13 versus 5.47 years, 95% CI, 1.7-8.5, p=0.0003), and cerebrospinal fluids more likely positive (p = 0.0181). All GAS and GBS were sensitive to penicillin (CLSI: MICs 0.06 - 2.0 µg/mL), with the majority of GAS sensitive to clindamycin and erythromycin, and half of the GBS resistant to clindamycin and erythromycin. Co-infections were prevalent, but viruses were only isolated with GAS (p=0.024). Isolation of GAS and GBS was associated with nearly 40% mortality and high rates of mechanical ventilation and inotropic supports. All non-survivors had high mortality (PIM2) and sepsis scores. CONCLUSIONS: Severe GAS and GBS are rare but associated with high mortality and rates of mechanical ventilation and inotropic supports in PICU. The streptococci are invariably sensitive to penicillin. The high PIM2 and Sepsis scores suggest that prompt recognition of sepsis and the timely judicious institution of antibiotics and intensive care support may be life-saving for these devastating infections.

Oncogenes without a Neighboring Tumor-Suppressor Gene Are More Prone to Amplification.

Focal copy number gains or losses are important genomic hallmarks of cancer. The genomic distribution of oncogenes and tumor-suppressor genes (TSG) in relation to focal copy number aberrations is unclear. Our analysis revealed that the mean distance of TSGs from oncogenes was significantly shorter than that of noncancer genes, suggesting that oncogenes and TSGs tend to be in close physical proximity in the human genome. Such relationship was conserved in mouse and drosophila. Pan-cancer analysis using data from The Cancer Genome Atlas indicated that oncogenes without a nearby TSG are more prone to amplification. In conclusion, our study provides evidence for the nonrandom distribution of oncogenes and TSGs across different species. Our data also support that the existence of a neighboring TSG can suppress amplification of an oncogene, shedding new light on a previously unappreciated protective mechanism of TSGs.