Pathogenicity locus, core genome, and accessory gene contributions to Clostridium difficile virulence

Clostridium difficile is a spore-forming anaerobic bacterium that causes colitis in patients with disrupted colonic microbiota. While some individuals are asymptomatic C. difficile carriers, symptomatic disease ranges from mild diarrhea to potentially lethal toxic megacolon. The wide disease spectrum has been attributed to the infected host’s age, underlying diseases, immune status, and microbiome composition. However, strain-specific differences in C. difficile virulence have also been implicated in determining colitis severity. Because patients infected with C. difficile are unique in terms of medical history, microbiome composition, and immune competence, determining the relative contribution of C. difficile virulence to disease severity has been challenging, and conclusions regarding the virulence of specific strains have been inconsistent. To address this, we used a mouse model to test 33 clinical C. difficile strains isolated from patients with disease severities ranging from asymptomatic carriage to severe colitis, and we determined their relative in vivo virulence in genetically identical, antibiotic-pretreated mice. We found that murine infections with C. difficile clade 2 strains (including multilocus sequence type 1/ribotype 027) were associated with higher lethality and that C. difficile strains associated with greater human disease severity caused more severe disease in mice. While toxin production was not strongly correlated with in vivo colonic pathology, the ability of C. difficile strains to grow in the presence of secondary bile acids was associated with greater disease severity. Whole-genome sequencing and identification of core and accessory genes identified a subset of accessory genes that distinguish high-virulence from lower-virulence C. difficile strains

Microbiome restoration by RBX2660 does not preclude recurrence of multidrug-resistant urinary tract infection following subsequent antibiotic exposure: A case report

A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens

Clinical Significance of Methicillin-Resistant Staphylococcus aureus Colonization on Hospital Admission: One-Year Infection Risk

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization among inpatients is a well-established risk factor for MRSA infection during the same hospitalization, but the long-term risk of MRSA infection is uncertain. We performed a retrospective cohort study to determine the one-year risk of MRSA infection among inpatients with MRSA-positive nasal polymerase chain reaction (PCR) tests confirmed by positive nasal culture (Group 1), patients with positive nasal PCR but negative nasal culture (Group 2), and patients with negative nasal PCR (Group 3). METHODOLOGY/PRINCIPAL FINDINGS: Subjects were adults admitted to a four-hospital system between November 1, 2006 and March 31, 2011, comprising 195,255 admissions. Patients underwent nasal swab for MRSA PCR upon admission; if positive, nasal culture for MRSA was performed; if recovered, MRSA was tested for Panton-Valentine Leukocidin (PVL). Outcomes included MRSA-positive clinical culture and skin and soft tissue infection (SSTI). Group 1 patients had a one-year risk of MRSA-positive clinical culture of 8.0% compared with 3.0% for Group 2 patients, and 0.6% for Group 3 patients (p<0.001). In a multivariable model, the hazard ratios for future MRSA-positive clinical culture were 6.52 (95% CI, 5.57 to 7.64) for Group 1 and 3.40 (95% CI, 2.70 to 4.27) for Group 2, compared with Group 3 (p<0.0001). History of MRSA and concurrent MRSA-positive clinical culture were significant risk factors for future MRSA-positive clinical culture. Group 1 patients colonized with PVL-positive MRSA had a one-year risk of MRSA-positive clinical culture of 10.1%, and a one-year risk of MRSA-positive clinical culture or SSTI diagnosis of 21.7%, compared with risks of 7.1% and 12.5%, respectively, for patients colonized with PVL-negative MRSA (p = 0.04, p = 0.005, respectively). CONCLUSIONS/SIGNIFICANCE: MRSA nasal colonization is a significant risk factor for future MRSA infection; more so if detected by culture than PCR. Colonization with PVL-positive MRSA is associated with greater risk than PVL-negative MRSA