Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Risk Factors for Recurrence of Clostridioides difficile in Hospitalized Patients.

BACKGROUND: Diarrhea and pseudomembranous colitis associated with Clostridioides difficile - a spore-forming anaerobic Gram-positive bacillus - is a major infection in hospitalized patients with a profound impact on clinical and economic outcomes. Recurrence (rCDI) is common and predisposes to further episodes with poor outcomes. METHOD: We aimed to identify a wide range of risk factors for recurrence to guide stewardship initiatives. After ethical approval, we commenced collecting demographic and clinical data of patients older than 18 years with clinically and microbiologically confirmed C. difficile infection. Data were statistically analyzed using R software. RESULTS: Of 204 patients included in the analysis, 36 (18%) suffered 90-day recurrence, rCDI was higher among females (23%) compared to males (13%), overall age median (IQR) was 66 (51-77), and for rCDI cases 81 (69-86) years. Among 26 variables analyzed to evaluate their association with rCDI, prior clindamycin exposure, concurrent use of aztreonam, patients >76 years, total hospital length of stay, and LOS before diagnosis ≤7 days, WBC ≤ 9.85 × 103 at discharge were more likely to experience rCDI. CONCLUSION: As identified in this analysis, patients with risk factors for rCDI could be candidates for close monitoring, a high index of suspicion, and risk mitigation interventions to avoid rCDI and improve clinical outcomes.

Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative.

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference -0.022, 90% confidence interval: -0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

Impact of Delayed Oral Vancomycin for Severe Clostridium difficile Infection.

Background: Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (VAN) is known to be superior to treatment with metronidazole (MDZ). However, previous studies have not evaluated the impact on patients when oral VAN therapy is delayed after diagnosis of severe CDI. Materials and Methods: This was a single-center, retrospective study of adult patients who were diagnosed with severe CDI. The objective was to compare clinical outcomes for patients treated initially with oral VAN versus patients receiving delayed oral VAN after at least 48 hours of initial treatment with MDZ. The primary outcome was all-cause in-hospital mortality. Results: There were 101 patients who comprised the initial oral VAN group, while 20 patients comprised the delayed oral VAN group. There was no significant difference in all-cause in-hospital mortality for patients in the initial oral VAN treatment group compared to those who had delayed oral VAN therapy (4.95% vs 15.00%, P = 0.13). Patients who were initially treated with oral VAN experienced a significantly higher rate of clinical cure (49.50% vs 20.00%, P = 0.02), shorter median postinfection length of hospitalization (7.0 days vs 13.0 days, P < 0.001), shorter median time to resolution of leukocytosis (3.9 days vs 10.4 days, P = 0.01), and were less likely to have an end of treatment serum creatinine greater than 1.5 times their baseline (8.7% vs 29.4%, P = 0.03). Conclusion: Patients who receive oral VAN as their initial treatment for severe CDI experience improved clinical outcomes compared to patients receiving delayed oral VAN after being initially treated with MDZ.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

BACKGROUND: A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. OBJECTIVE: To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. METHODS: This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m2), obesity class I and II (BMI 30-39.9kg/m2), and obesity class III (BMI≥40 kg/m2) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. RESULTS: Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). CONCLUSIONS: Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Comparison of ß-lactam plus aminoglycoside versus ß-lactam plus fluoroquinolone empirical therapy in serious nosocomial infections due to Gram-negative bacilli.

We sought to compare clinical cure on day 7 and a 28-day all-cause mortality in patients who received an anti-pseudomonal ß-lactam with a fluoroquinolone or an aminoglycoside for treatment of nosocomial bacteremia or pneumonia due to Gram-negative bacilli while in the ICU. This retrospective cohort study was conducted in critically ill patients at an academic medical centre from January 2005 to August 2011. A total of 129 patients (83 receiving aminoglycoside and 46 receiving fluoroquinolone combinations) were included. Seven-day clinical cure rates were 74% and 72% for fluoroquinolone and aminoglycoside groups, respectively (p = 0.84). There was no significant difference in the odds of clinical cure with a fluoroquinolone as compared to an aminoglycoside combination (adjusted odds ratio 2.4, 95% confidence interval [CI] 0.7-9.0). There was no significant difference in 28-day mortality in patients who received a fluoroquinolone or an aminoglycoside combination (22% vs. 18%, adjusted hazard ratio 0.82, 95% CI 0.29-2.28).

Variables Affecting Pharmacy Students' Patient Care Interventions during Advanced Pharmacy Practice Experiences.

Objective. To identify the temporal effect and factors associated with student pharmacist self-initiation of interventions during acute patient care advanced pharmacy practice experiences (APPE). Methods. During the APPE, student pharmacists at an academic medical center recorded their therapeutic interventions and who initiated the intervention throughout clinical rotations. At the end of the APPE student pharmacists completed a demographic survey. Results. Sixty-two student pharmacists were included. Factors associated with lower rates of self-initiated interventions were infectious diseases and pediatrics APPEs and an intention to pursue a postgraduate residency. Timing of the APPE, previous specialty elective course completion, and previous hospital experience did not result in any significant difference in self-initiated recommendations. Conclusion. Preceptors should not base practice experience expectations for self-initiated interventions on previous student experience or future intentions. Additionally, factors leading to lower rates of self-initiated interventions on infectious diseases or pediatrics APPEs should be explored.

Fulminant Invasive Pulmonary Aspergillosis After a Near-Drowning Accident in an Immunocompetent Patient.

OBJECTIVE: To report on invasive aspergillosis infection in an immunocompetent adult after a near-drowning event, which allowed this pathogen to easily gain access to the human respiratory system and result in rapid, severe infection. CASE SUMMARY: A 51-year-old female developed severe pneumonia after a near-drowning accident. Two days after admission, a bronchial alveolar lavage (BAL) was performed and was positive for Aspergillus fumigatus. After a 30-day hospital course, multiple antifungals, and various routes of administration, the patient expired. DISCUSSION:: Pneumonia is particularly common because of the aspiration of contaminated water. Whereas pneumococci, staphylococci, and Gram-negative bacteria are all common pathogens for this type of infection, fungi such as Aspergillus spp can also be involved and may be life threatening. Typically, these cases are reported in individuals with an immunodeficiency such as from receipt of myelosuppressive chemotherapy, bone marrow transplants, or lung transplants. Despite initiation of an appropriate empirical antifungal regimen, the rapid recovery of A fumigatus from pulmonary alveolar lavage and BAL samples as well as extremely elevated levels of galactomannan and (1→3)-ß-D glucan may have indicated an invasive fungal infection (IFI). CONCLUSION:: IFIs are uncommon in immunocompetent adults, but in the event of a near-drowning accident, environmental fungi can gain access to the human respiratory system and result in rapid, severe infection. Based on this case and the others described, it appears that near-drowning patients need an early initial evaluation for IFI.