Enhanced Clostridioides difficile Infection Prevention With a Pharmacy-Controlled Policy That Adds a 3-Strain Lactobacillus Probiotic Concomitantly to Antibiotic Therapy.

When 70% of antibiotic users took a 3-strain Lactobacillus probiotic preparation the hospital-wide rate of healthcare-associated Clostridioides difficile infection improved significantly. The incidence of C. difficile infection for those taking the probiotic along with multiple antibiotics or a single high-risk antibiotic was decreased by at least half.

Clostridioides difficile infection in a skilled nursing facility (SNF): cost savings of an automated, standardized probiotic antimicrobial stewardship programme (ASP) policy.

Background: With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course. Objectives: To assess the value of providing probiotic therapy to SNF patients at risk for CDI. Patients and methods: Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness. Results: From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16-0.31) to 4, OR = 0.08 (0.03-0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544-$154 085. Conclusions: With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective.

The Acid-Dependent and Independent Effects of Lactobacillus acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 on Clostridioides difficile R20291.

Clostridioides difficile infections (CDI) result from antibiotic use and cause severe diarrhea which is life threatening and costly. A specific probiotic containing Lactobacillus acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 has demonstrated a strong inhibitory effect on the growth of several nosocomial C. difficile strains by production of antimicrobial metabolites during fermentation. Though there are several lactobacilli shown to inhibit C. difficile growth by processes relying on acidification, this probiotic has demonstrated potency for CDI prevention among hospitalized patients. Here, we describe the acid-dependent and independent mechanisms by which these strains impair the cytotoxicity of a hypervirulent strain, C. difficile R20291 (CD). These bacteria were co-cultured in a series of experiments under anaerobic conditions in glucose-rich and no-sugar medium to inhibit or stimulate CD toxin production, respectively. In glucose-rich medium, there was low CD toxin production, but sufficient amounts to cause cytotoxic damage to human fibroblast cells. In co-culture, there was acidification by the lactobacilli resulting in growth inhibition as well as ≥ 99% reduced toxin A and B production and no observable cytotoxicity. In the absence of glucose, CD produced much more toxin. In co-culture, the lactobacilli did not acidify the medium and CD growth was unaffected; yet, the amount of detected toxin A and B was decreased by 20% and 41%, respectively. Despite the high concentration of toxin, cells exposed to the supernatant from the co-culture were able to survive. These results suggest that in addition to known acid-dependent effects, the combination of L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 can interfere with CD pathogenesis without acidification: (1) reduced toxin A and B production and (2) toxin neutralization. This might explain the strain specificity of this probiotic in potently preventing C. difficile-associated diarrhea in antibiotic-treated patients compared with other probiotic formulae.

Role of haptoglobin on the uptake of native and beta-chain [trimesoyl-(Lys82)beta-(Lys82)beta] cross-linked human hemoglobins in isolated perfused rat livers.

The role of haptoglobin in liver cell entry of acellular native hemoglobin, and cross-linked human hemoglobin, a potentially useful oxygen-carrier alternative in transfusion medicine, was examined in the recirculating, perfused rat liver preparation. Doses of tritiated native human or beta-chain [trimesoyl-(Lys82)beta-(Lys82)beta] cross-linked human hemoglobin were preincubated with haptoglobin-containing rat plasma or Krebs Henseleit bicarbonate buffer for 30 min and used for perfusion. Concentrations (dpm/ml) in reservoir, before and after separation of the hemoglobins and metabolites by gel filtration fast protein liquid chromatography column chromatography, were similar, showing mostly the presence of intact hemoglobin. Each hemoglobin species underwent a rapid distribution phase, followed by a protracted elimination phase. The radioactivity in bile at 3 h consisted of low molecular weight metabolites, and cumulative excretion was slightly higher when rat plasma was present: for native hemoglobin, 7.1 +/- 1.6% versus 9.2 +/- 2.1% dose; for cross-linked hemoglobin, 5.0 +/- 1.7% versus 7.2 +/- 0.8% dose. Data fit to a two-compartment model and physiologically based model revealed a significantly faster influx clearance (CL(influx)) over the metabolic intrinsic clearance (CL(int, met)). The ratios of CL(influx)/CL(int, met) were 125 and 535 for native hemoglobin in the absence and presence of rat haptoglobin, respectively, according to compartmental analyses; the ratios were 25 and 53, respectively, according to physiological modeling. The corresponding ratios for cross-linked hemoglobin in the absence and presence of rat haptoglobin were 55 and 81, respectively, and 24 and 70 for compartmental and physiological modeling. Although haptoglobin enhanced the hepatic internalization of the hemoglobins, the impact on the net clearance was lessened since degradation was the rate-limiting step.

Investigating the therapeutic potential of a probiotic in a clinical population with chronic hand dermatitis.

BACKGROUND: Hand dermatitis or hand eczema (HD) is one of the most common dermatologic conditions. Lesions, scaling, pruritus and pain are chronic and relapsing. Improved HD has been reported with the probiotic composed of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 (Bio-K+). PURPOSE: Investigation of the therapeutic potential of this probiotic as the sole systemic treatment for adults with nonacute HD. SUBJECTS AND METHODS: A single-center study documented clinical ratings and patient-reported outcomes in adults with chronic HD. The probiotic was taken orally for 12 weeks, adjunctive to standard topical treatments and preventative measures. RESULTS: Most of the 30 subjects with mild to severe HD were compliant with the probiotic. Around 22 of the 30 subjects were able to complete the study, and of these subjects, an improvement was noted in 19. One required systemic therapy, and one subject was not able to tolerate the probiotic and therefore discontinued the study. 23% of the subjects achieved clear or almost clear hands by the end of 12 weeks. Pruritus, which was a common complaint at baseline, was improved with 59% of symptomatic patients within 2 weeks. CONCLUSION: It is feasible and safe to administer Bio-K+ for HD. Clinicians saw an improvement in most subjects' hands, and cases of significant improvement in dermatitis were documented. Pruritus was the most rapidly relieved symptom, as reported by patients.

Binding of acellular, native and cross-linked human hemoglobins to haptoglobin: enhanced distribution and clearance in the rat.

It is well established that hemoglobin resulting from red cell lysis binds to haptoglobin in plasma to form a complex. The increased molecular size precludes its filtration by the kidneys, redirecting it toward hepatocellular entry. Chemically cross-linked hemoglobins are designed to be resistant to renal excretion, even in the absence of haptoglobin. The manner in which binding to haptoglobin influences the pharmacokinetics of acellular cross-linked and native hemoglobins was investigated after intravenous injection of radiolabeled native human hemoglobin and trimesyl-(Lys82)beta-(Lys82)beta cross-linked human hemoglobin, at trace doses, into rats. Under these conditions, there is sufficient plasma haptoglobin for binding with hemoglobin. In vitro binding assayed by size-exclusion chromatography for bound and free hemoglobin revealed that, at <8 muM hemoglobin, native human hemoglobin was completely bound to rat haptoglobin, whereas only approximately 30% of trimesyl-(Lys82)beta-(Lys82)beta cross-linked hemoglobin was bound. Plasma disappearance of low doses (0.31 mumol/kg) of native and cross-linked hemoglobins was monoexponential (half-life = 23 and 33 min, respectively). The volume of distribution (40 vs. 19 ml/kg) and plasma clearance (1.22 vs. 0.4 ml.min(-1).kg(-1)) were higher for native than for cross-linked hemoglobin. Native and cross-linked human hemoglobins were found primarily in the liver, and not in the kidney, heart, lung, or spleen, mostly as degradation products. These pharmacokinetic findings suggest that the binding of hemoglobin to haptoglobin enhances its hepatocellular entry, clearance, and distribution.

Rates of release of nitric oxide from HbSNO and internal electron transfer.

The discovery that hemoglobin (Hb) in erythrocytes contains a fraction of beta-Cys-93 thiols as the nitrosylated derivative (HbSNO) led to the suggestion that this species is involved in transporting and releasing nitric oxide, which is the signal for local vasodilation. The release of NO from HbSNO requires an electron transfer to facilitate release and to regenerate the cysteine thiol via one-electron reduction in the absence of added thiols. An alternative mechanism, which has received much attention, transfers the nitrosyl group to an external thiol, which in turn would have to be reduced. The observed first order rate constant for the spontaneous oxidation of the ferrous heme of deoxy HbSNO is 1.0 x 10(-4)s(-1) in the absence of thiols. Under the same conditions, native Hb is stable. The oxidation of HbSNO occurs with the same rate constant that can be derived for the rate reported for the formation of HbNO from HbSNO. These similarities suggest that both processes involve the same reaction: internal electron transfer and direct release of nitric oxide.