First-line Vancomycin Research Articles

Cost-Effectiveness Analysis of Antimicrobial Prescribing in the Treatment of Clostridioides Difficile Infection in England.

An economic model was developed with guidance from the National Institute for Health and Care Excellence (NICE) 'Managing Common Infections' (MCI) Committee to evaluate the cost effectiveness of different antibiotic treatment sequences for treating Clostridioides difficile infection (CDI) in England. The model consisted of a 90-day decision tree followed by a lifetime cohort Markov model. Efficacy data were taken from a network meta-analysis and published literature, while cost, utility and mortality data were taken from published literature. A treatment sequence was defined as a first-line intervention or a different second-line intervention, and used constant third- and fourth-line interventions. The possible first- and second-line interventions were vancomycin, metronidazole, teicoplanin and fidaxomicin (standard and extended regimens). Total costs and quality-adjusted life-years (QALYs) were calculated and were used to run a fully incremental cost-effectiveness analysis. Threshold analysis was conducted around pricing. Sequences including teicoplanin, fidaxomicin (extended regimen) and second-line metronidazole were excluded based on recommendations from the committee. The final pairwise comparison was between first-line vancomycin and second-line fidaxomicin (VAN-FID), and the reverse (FID-VAN). The incremental cost-effectiveness ratio for FID-VAN compared with VAN-FID was £156,000 per QALY gained, and FID-VAN had a 0.2% likelihood of being cost effective at a £20,000 threshold. First-line vancomycin and second-line fidaxomicin was the most cost-effective treatment sequence at the NICE threshold for treating CDI in England. The main limitation of this study was that the initial cure and recurrence rates of each intervention were applied constantly across each line of treatment and each round of recurrence.

Risk Factors and Outcome of C. difficile Infection after Hematopoietic Stem Cell Transplantation.

Patients who undergo hematopoietic stem cell transplants (HSCT) are at major risk of C. difficile (CD) infection (CDI), the most common cause of nosocomial diarrhea. We conducted a retrospective study, which enrolled 481 patients who underwent autologous (220) or allogeneic HSCT (261) in a 5-year period, with the aim of identifying the incidence, risk factors and outcome of CDI between the start of conditioning and 100 days after HSCT. The overall cumulative incidence of CDI based upon clinical evidence was 5.4% (95% CI, 3.7% to 7.8%), without any significant difference between the two types of procedures. The median time between HSCT and CDI diagnosis was 12 days. Out of 26 patients, 19 (73%) with clinical and symptomatic evidence of CDI were positive also for enzymatic or molecular detection of toxigenic CD; in particular, in 5 out of 26 patients (19%) CD binary toxin was also detected. CDI diagnoses significantly increased in the period 2018–2019, since the introduction in the microbiology lab unit of the two-step diagnostic test based on GDH immunoenzymatic detection and toxin B/binary toxin/027 ribotype detection by real-time PCR. Via multivariate analysis, abdominal surgery within 10 years before HSCT (p = 0.002), antibiotic therapy within two months before HSCT (p = 0.000), HCV infection (p = 0.023) and occurrence of bacterial or fungal infections up to 100 days after HSCT (p = 0.003) were significantly associated with a higher risk of CDI development. The 26 patients were treated with first-line vancomycin (24) or fidaxomicine (2) and only 2 patients needed a second-line treatment, due to the persistence of stool positivity. No significant relationship was identified between CDI and the development of acute graft versus host disease (GVHD) after allogeneic HSCT. At a median follow-up of 25 months (range 1–65), the cumulative incidence of transplant related mortality (TRM) was 16.6% (95% CI 11.7% to 22.4%) and the 3-year overall survival (OS) was 67.0% (95% CI 61.9% to 71.6%). The development of CDI had no significant impact on TRM and OS, which were significantly impaired in the multivariate analysis by gastrointestinal and urogenital comorbidities, severe GVHD, previous infections or hospitalization within two months before HSCT, active disease at transplant and occurrence of infections after HSCT. We conclude that 20% of all episodes of diarrhea occurring up to 100 days after HSCT were related to toxigenic CD infection. Patients with a history of previous abdominal surgery or HCV infection, or those who had received broad spectrum parenteral antibacterial therapy were at major risk for CDI development. CDIs were successfully treated with vancomycin or fidaxomicin after auto-HSCT as well as after allo-HSCT.

Is First-Line Vancomycin Still the Best Option to Treat Staphylococcus Health Care–Associated Meningitis?

Cerebrospinal fluid (CSF) penetration of vancomycin through the blood-brain barrier is poor but important inflammation improved it. Hence, vancomycin is recommended for the treatment of community meningitis. However, what about mild inflammatory health care-associated meningitis? The aim of this study was to evaluate the impact of vancomycin diffusion on CSF in Staphylococcus epidermidis health care-associated meningitis. This was a retrospective study of all consecutive patients with S.epidermidis CSF shunt-associated infection, which was treated by continuous intravenous vancomycin after standard of care (60 mg/kg/d after a loading dose of 15 mg/kg). Patient outcome, CSF protein level, and vancomycin concentration in CSF and serum were assessed. We report 6 consecutives cases. Clinical and biologic manifestations were of mild intensity. Meningeal permeability was moderately altered with low CSF protein levels. Despite appropriate vancomycin dosage resulting in high serum concentrations, CSF remained below the S.epidermidis minimal inhibitory concentration. We propose to reassess vancomycin use as first-line therapy when meningeal inflammation is mild-to-moderate in favor of antibiotics, which have a better CSF penetration.

Early Infectious Complications after High-Dose Therapy and Autologous Blood Stem Cell Transplantation

Background: Only few data have been published regarding the frequency and type of infectious complications after high-dose therapy (HDT) and autologous blood stem cell transplantation (ASCT). The purpose of this study was to evaluate early infectious complications after this type of treatment and to identify predictive factors. Patients and Methods: The clinical data of 100 patients (50 with hematologic neoplasms, 50 with solid tumors) treated with 133 HDT-courses in a single institution were analyzed retrospectively. For 34 courses CD34+ cells were positively enriched. Results: In 86% of the courses fever occurred during neutropenia. In response to an empirical antibiotic therapy with ceftazidime and either vancomycin or flucloxacillin the patients defervesced after a median of 3 days. No invasive fungal infection was diagnosed. There was no infection-related death. Comparing hematologic neoplasms and solid tumors, a significant difference in the duration of fever was found: median 4 vs. 2 days. We observed a correlation between the duration of fever and the duration of morphin needing mucositis. Apart from a group of ‘myeloablative’ busulfan- and/or TBI-containing regimens we separated two different aggressive groups of HDT-regimens using duration of severe neutropenia and morphine-needing mucositis. A multivariate analysis demonstrated that the type of HDT-regimen is a predictive factor for the number of fever days and freedom from infection. The diagnosis (hematologic neoplasia vs. solid tumor) is predictive only for pneumonia/ pneumonitis. Conclusion: Early infectious complications after HDT and ASCT are usually not severe. The application of first-line vancomycin and amphotericin B is generally not necessary. The type of HDT-regimen has to be considered in further prospective investigations of predictive infection-related factors.