Multiple Lactobacillus Infections Caused by Probiotics at Pediatric and Adult Academic Medical Centers.

BACKGROUND: Probiotics are synthetic oral supplements containing live bacterial and fungal species hypothesized to help with various gastrointestinal conditions. However, they can cause infection if the organism spreads outside of the gastrointestinal tract. The aim of this study was to identify and describe patients who experienced systemic infections caused by probiotic use. METHODS: This study was a retrospective chart review of pediatric and adult patients at academic medical centers who received probiotics and subsequently developed positive cultures from a sterile site for probiotic-related species. Two individuals completed the chart reviews to determine if the probiotic was the true cause of the infection. RESULTS: Lactobacillus, Bifidobacterium, and Saccharomyces cultures were reviewed, with a total of 71, 8, and 2 cultures isolated from sterile sites for each organism, respectively. Further review revealed 23 Lactobacillus cultures from 13 unique patients who were taking Lactobacillus-containing probiotics. Four patients without gastrointestinal tract compromise were included in the final analysis, including 1 patient whose culture was confirmed as identical to the probiotic. Types of infections included meningitis and bacteremia. Targeted antimicrobial therapy included ampicillin, ampicillin-sulbactam, and piperacillin-tazobactam, with total durations of therapy ranging from 10 to 22 days. No patients had mortality attributed to Lactobacillus infection. CONCLUSIONS: Probiotics are not harmless supplements as they come with risk of serious infection as demonstrated in this review. Before use, the risks of probiotics should be considered carefully for each individual patient. Clinicians should consider avoiding probiotics in hospitalized patients, especially those with vascular or extra-ventricular access devices.

Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.

IMPORTANCE: Staphylococcus saprophyticus is the second most common bacteria associated with urinary tract infections (UTIs) in women. The antimicrobial treatment regimen for uncomplicated UTI is normally nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), or a fluoroquinolone without routine susceptibility testing of S. saprophyticus recovered from urine specimens. However, TMP-SMX-resistant S. saprophyticus has been detected recently in UTI patients, as well as in our cohort. Herein, we investigated the understudied resistance patterns of this pathogenic species by linking genomic antibiotic resistance gene (ARG) content to susceptibility phenotypes. We describe ARG associations with known and novel SCCmec configurations as well as phage elements in S. saprophyticus, which may serve as intervention or diagnostic targets to limit resistance transmission. Our analyses yielded a comprehensive database of phenotypic data associated with the ARG sequence in clinical S. saprophyticus isolates, which will be crucial for resistance surveillance and prediction to enable precise diagnosis and effective treatment of S. saprophyticus UTIs.

Small Molecule Chelators Reveal That Iron Starvation Inhibits Late Stages of Bacterial Cytokinesis.

Bacterial cell division requires identification of the division site, assembly of the division machinery, and constriction of the cell envelope. These processes are regulated in response to several cellular and environmental signals. Here, we use small molecule iron chelators to characterize the surprising connections between bacterial iron homeostasis and cell division. We demonstrate that iron starvation downregulates the transcription of genes encoding proteins involved in cell division, reduces protein biosynthesis, and prevents correct positioning of the division machinery at the division site. These combined events arrest the constriction of the cell during late stages of cytokinesis in a manner distinct from known mechanisms of inhibiting cell division. Overexpression of genes encoding cell division proteins or iron transporters partially suppresses the biological activity of iron chelators and restores growth and division. We propose a model demonstrating the effect of iron availability on the regulatory mechanisms coordinating division in response to the nutritional state of the cell.

Targeting quinolone- and aminocoumarin-resistant bacteria with new gyramide analogs that inhibit DNA gyrase.

Bacterial DNA gyrase is an essential type II topoisomerase that enables cells to overcome topological barriers encountered during replication, transcription, recombination, and repair. This enzyme is ubiquitous in bacteria and represents an important clinical target for antibacterial therapy. In this paper we report the characterization of three exciting new gyramide analogs-from a library of 183 derivatives-that are potent inhibitors of DNA gyrase and are active against clinical strains of gram-negative bacteria (Escherichia coli, Shigella flexneri, and Salmonella enterica; 3 of 10 wild-type strains tested) and gram-positive bacteria (Bacillus spp., Enterococcus spp., Staphylococcus spp., and Streptococcus spp.; all 9 of the wild-type strains tested). E. coli strains resistant to the DNA gyrase inhibitors ciprofloxacin and novobiocin display very little cross-resistance to these new gyramides. In vitro studies demonstrate that the new analogs are potent inhibitors of the DNA supercoiling activity of DNA gyrase (IC50s of 47-170 nM) but do not alter the enzyme's ATPase activity. Although mutations that confer bacterial cells resistant to these new gyramides map to the genes encoding the subunits of the DNA gyrase (gyrA and gyrB genes), overexpression of GyrA, GyrB, or GyrA and GyrB together does not suppress the inhibitory effect of the gyramides. These observations support the hypothesis that the gyramides inhibit DNA gyrase using a mechanism that is unique from other known inhibitors.