Impact of Clostridioides difficile length of treatment on rates of recurrence in patients on concurrent antibiotics.

BACKGROUND: Clostridioides difficile infection (CDI) is principally health care-associated, with a substantial impact on morbidity and mortality. The guidelines recommend CDI therapy for 10 days; however, it is often extended in practice when concurrent antibiotics are used. The impact of the extended duration of therapy remains unclear. OBJECTIVE: To compare the rates of CDI recurrence in patients receiving standard duration of therapy (SDT) with those receiving extended duration of therapy (EDT) for the treatment of hospital-acquired CDI (HA-CDI) while receiving concurrent antibiotics. METHODS: A retrospective chart review was conducted between October 2017 and 2019. Adult HA-CDI patients who received a minimum 10 days of CDI therapy and were on concurrent antibiotics were stratified into SDT and EDT groups. Rates of CDI recurrence (at 90 and 180 days) and incidence of new-onset vancomycin-resistant enterococcus (VRE) were compared. RESULTS: Two hundred twenty-three patients met the inclusion criteria (SD-106, EDT-117). CDI recurrence rates at 90 and 180 days were not statistically significant between SDT and EDT groups (22% vs 26%, P = .40% and 26% vs 31%, P = .47). Although the incidence of VRE within the extended group was higher, it was not statistically significant (6% vs 9%, P = .29). CONCLUSIONS: No significant difference in rates of recurrence or new-onset VRE was observed between SDT and EDT in HA-CDI patients.

Pilot study evaluating intravenous amoxicillin-clavulanate as an alternative to piperacillin-tazobactam for general surgery patients.

In this point-prevalence survey followed by prospective audit and feedback at 4 tertiary-care hospitals in Calgary, Alberta, Canada, we evaluated whether intravenous amoxicillin-clavulanate may be used as a narrower-spectrum alternative to intravenous piperacillin-tazobactam for patients admitted to general surgery services.

Levofloxacin for febrile neutropenia prophylaxis in acute myeloid leukemia patients associated with reduction in hospital admissions.

PURPOSE: The purpose of this study is to evaluate the efficacy and safety of prophylactic oral levofloxacin in acute myeloid leukemia (AML) patients after receiving consolidation chemotherapy to prevent febrile neutropenia. METHODS: We conducted a retrospective chart review of 50 AML patients who were prescribed levofloxacin and 50 AML patients who were not prescribed levofloxacin post-consolidation chemotherapy between June 2006 and August 2013 at a tertiary academic medical center. The primary outcome of this study was to evaluate the effectiveness of levofloxacin in preventing hospital readmission due to febrile neutropenia. Secondary outcomes evaluated the safety of this therapy, including the rate of Clostridium difficile-associated diarrhea (CDAD) within 30 days from discharge of receiving consolidation chemotherapy and rate of fluoroquinolone resistance in positive bacterial cultures. RESULTS: Hospital readmission due to febrile neutropenia after the first consolidation cycle occurred in 42% of patients prescribed levofloxacin, as compared to 72% that were not prescribed levofloxacin (p = 0.002). This was also significantly reduced when levofloxacin was prescribed after all consolidation cycles (51.4 vs. 67%, p = 0.023). CDAD did not occur in any patient prescribed levofloxacin after the first cycle, compared to one case in those not prescribed levofloxacin. Evaluation of the impact on fluoroquinolone resistance was limited due to a paucity of fluoroquinolone susceptibilities reported. CONCLUSIONS: Prescribing oral levofloxacin post-consolidation chemotherapy in AML patients is associated with a reduction in febrile neutropenia. Further research is required to identify the impact on fluoroquinolone resistance and risk of CDAD.

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

High-dose methotrexate in adult oncology patients: a case-control study assessing the risk association between drug interactions and methotrexate toxicity.

INTRODUCTION: High-dose methotrexate, defined as dose ≥1 g/m(2), is commonly used in chemotherapy protocols. Certain drugs such as acyclovir, allopurinol, proton pump inhibitors and some antibiotics have been associated with delayed renal clearance of methotrexate and may predispose patients to toxicities. Currently, no specific recommendations exist on adjusting the high-dose methotrexate regimen in the presence of potential interacting drugs. This study aims to determine whether presence of interacting drugs is associated with delayed methotrexate clearance. METHODS: This was a case-control study of adult oncology patients who received their first cycle of high-dose methotrexate. Cases were defined as patients who experienced delayed methotrexate clearance, as indicated by serum methotrexate level ≥ 0.1 umol/L at 72 h. The primary endpoint was the frequency of presence of interacting drugs between cases and controls. These were compared using Fisher's exact test. Where possible, adjustment for significant baseline differences that can affect methotrexate clearance was made using logistic regression. The secondary endpoint was frequency of methotrexate-related clinical toxicities between groups and included myelosuppression, nephrotoxicity, hepatotoxicity and mucositis. RESULTS: From January 2004 to March 2011, 73 patients met study criteria, of which 23 were defined as cases. Significant baseline differences were methotrexate dose received (9116 mg ± 4339 versus 6054 mg ± 2874, p=0.012) and renal impairment (5 versus 0, p = 0.002). The presence of interacting drugs was not associated with delayed methotrexate clearance (OR 0.91, 95% CI 0.24-3.38, p > 0.999). After adjusting for methotrexate dose, drugs observed more frequently (allopurinol, proton pump inhibitors and sulfamethoxazole/trimethoprim) were not associated with delayed methotrexate clearance (p = 0.95, 0.59 and 0.20, respectively). Cases experienced more severe anemia (grade 2.52 versus 1.68, p = 0.007) and higher rates of mucositis (65.2% versus 20.0%, p < 0.001). CONCLUSION: This study showed no significant association between presence of interacting drugs and delayed methotrexate clearance. Patients who experienced delayed methotrexate clearance had higher incidence of severe anemia and mucositis.

Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism.

Mutations in the fibrillin-1 gene give rise to a number of heritable disorders, which are all characterized by various malformations of bone as well as manifestations in other tissues. However, the role of fibrillin-1 in the development and homeostasis of bone is not well understood. Here, we examined the role of fibrillin-1 in regulating osteoclast differentiation from primary bone-marrow-derived precursors and monocytic RAW 264.7 cells. The soluble N-terminal half of fibrillin-1 (rFBN1-N) strongly inhibited osteoclastogenesis, whereas the C-terminal half (rFBN1-C) did not. By contrast, when rFBN1-N was immobilized on calcium phosphate, it did not affect osteoclastogenesis but modulated osteoclast resorptive activity, which was evident by a larger number of smaller resorption pits. Using a panel of recombinant sub-fragments spanning rFBN1-N, we localized an osteoclast inhibitory activity to the 63 kDa subfragment rF23 comprising the N-terminal region of fibrillin-1. Osteoclastic resorption led to the generation of small fibrillin-1 fragments that were similar to those identified in human vertebral bone extracts. rF23, but not rFBN1-N, was found to inhibit the expression of cathepsin K, matrix metalloproteinase 9 and Dcstamp in differentiating osteoclasts. rFBN1-N, but not rF23, exhibited interaction with RANKL. Excess RANKL rescued the inhibition of osteoclastogenesis by rFBN1-N. By contrast, rF23 disrupted RANKL-induced Ca(2+) signaling and activation of transcription factor NFATc1. These studies highlight a direct dual inhibitory role of N-terminal fibrillin-1 fragments in osteoclastogenesis, the sequestration of RANKL and the inhibition of NFATc1 signaling, demonstrating that osteoclastic degradation of fibrillin-1 provides a potent negative feedback that limits osteoclast formation and function.