Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria

Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of large sets of clinical bacterial isolates has greatly expanded our understanding of how antibiotic resistance develops and transmits among bacteria and between patients. Diverse mechanisms of resistance, including antibiotic degradation, antibiotic target modification, and modulation of permeability through the bacterial membrane have been demonstrated. These fundamental insights into the mechanisms of gram-negative antibiotic resistance have influenced the development of novel antibiotics and treatment practices in highly resistant infections. Here, we review the mechanisms and global epidemiology of antibiotic resistance in some of the most clinically important resistance phenotypes, including carbapenem resistant Enterobacteriaceae, extensively drug resistant (XDR) Pseudomonas aeruginosa, and XDR Acinetobacter baumannii. Understanding the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterials and for individual treatment decisions, which often involve alternatives to β-lactam antibiotics

The pandemic provides a pathway: What we know and what we need to know about using COVID positive donors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170875/1/tid13727.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170875/2/tid13727_am.pd

Low risk high reward: What should we worry about with coronavirus disease 2019 positive donors?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174836/1/tid13892_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174836/2/tid13892.pd

Staphylococcus aureus Prostatic Abscess in the Setting of Prolonged S. aureus Bacteremia

Staphylococcus aureus rarely causes prostatic abscess. We report five cases of S. aureus prostatic abscess in the setting of bacteremia at our institution that occurred between 12/2018 and 05/2019. Three of the cases were caused by MRSA, and four of the patients underwent drainage of the prostatic abscess. All five patients received a minimum of six weeks of antibiotic therapy. One of the five patients died during the course of their infection. S. aureus prostatic abscess with bacteremia is an uncommon but serious disease. Treatment should consist of a combination of prolonged antibiotic therapy and surgical drainage when feasible

Polymorphisms in Fibronectin Binding Proteins A and B among Staphylococcus aureus Bloodstream Isolates Are Not Associated with Arthroplasty Infection

Background Nonsynonymous single nucleotide polymorphisms (SNPs) in fibronectin binding protein A (fnbA) of Staphylococcus aureus are associated with cardiac device infections. However, the role of fnbA SNPs in S. aureus arthroplasty infection is unknown. Methods Bloodstream S. aureus isolates from a derivation cohort of patients at a single U.S. medical center with S. aureus bacteremia (SAB) and prosthetic hip or knee arthroplasties that were infected (PJI, n = 27) or uninfected (PJU, n = 43) underwent sequencing of fnbA and fnbB. A validation cohort of S. aureus bloodstream PJI (n = 12) and PJU (n = 58) isolates from Germany also underwent fnbA and fnbB sequencing. Results Overall, none of the individual fnbA or fnbB SNPs were significantly associated with the PJI or PJU clinical groups within the derivation cohort. Similarly, none of the individual fnbA or fnbB SNPs were associated with PJI or PJU when the analysis was restricted to patients with either early SAB (i.e., bacteremia occurring 1 year after placement or manipulation of prostheses). Conclusions In contrast to cardiac device infections, there is no association between nonsynonymous SNPs in fnbA or fnbB of bloodstream S. aureus isolates and arthroplasty infection. These results suggest that initial steps leading to S. aureus infection of cardiovascular and orthopedic prostheses may arise by distinct processes

Single Nucleotide Polymorphisms (SNPs) in fibronectin binding protein B (<i>fnbB)</i> in <i>fnbB-</i>containing isolates.

<p>*When false discovery rate control is applied, this raw p-value no longer maintains statistical significance (p = 1.00).</p><p>No SNP was associated with the prosthetic joint infected (PJI) or uninfected (PJU) isolates in the derivation cohort, external validation cohort, or late <i>S</i>. <i>aureus</i> bacteremia (SAB) group. Late SAB was defined as SAB occurring >1 year after placement or manipulation of prostheses.</p

Demographic and clinical characteristics of patients in the derivation cohort with <i>S</i>. <i>aureus</i> bacteremia and infected or uninfected prostheses.

<p>*Late infection is defined as bloodstream infection occurring >1 year after the prostheses was implanted or surgically manipulated.</p><p>Demographic and clinical characteristics of patients in the derivation cohort with <i>S</i>. <i>aureus</i> bacteremia and infected or uninfected prostheses.</p

Comparison of the biofilm-forming capacity of <i>S</i>. <i>aureus</i> isolates from prosthetic joint infection (PJI) and uninfected prosthetic joint (PJU) groups.

<p>Values were calculated as percentage capacity to form biofilms relative to <i>S</i>. <i>aureus</i> control strain UAMS-1. Box ends represent the 25^th and 75^th percentiles, and whisker ends represent the minimum and maximum. There was no difference in biofilm-forming capacity between isolates in the PJI and PJU groups.</p

Comparison of the fibronectin binding capacity of <i>S</i>. <i>aureus</i> isolates from prosthetic joint infection (PJI) and uninfected prosthetic joint (PJU) groups.

<p>Values were calculated as percentage capacity to bind fibronectin relative to <i>S</i>. <i>aureus</i> control strain 8325–4. Box ends represent the 25^th and 75^th percentiles, and whisker ends represent the minimum and maximum. There was no difference in fibronectin binding capacity between isolates in the PJI and PJU groups.</p

Single Nucleotide Polymorphisms (SNPs) in fibronectin binding protein A (<i>fnbA)</i> in the derivation cohort, external validation cohort, and late <i>S</i>. <i>aureus</i> bacteremia (SAB) group.

<p>*When false discovery rate control is applied, this raw p-value no longer maintains statistical significance (p = 0.22).</p><p>In the derivation cohort, no SNPs occurred with greater frequency in the prosthetic joint infection group (PJI) relative to the uninfected prosthetic joint group (PJU). In the external validation cohort, one SNP (S839N) was significantly associated with the PJU group, though when the two cohorts were combined the S839N association did not reach statistical significance (p = 0.22). Late SAB was defined as bacteremia occurring >1 year after placement or manipulation of prostheses, and here contains data from both the derivation and external validation cohorts. In the late SAB group, no SNPs occurred with greater frequency in PJI or PJU.</p