What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of Veterans with initial mild disease

Background: Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data is limited to guide clinicians in identifying these patients. Methods: Our two-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30-days post-treatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristic/s predictive of success identified in the first-stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results: Among 3,656 patients treated with metronidazole, we identified 3,282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI] 1.29 – 2.06) than age \u3e65 years. Among 115 propensity-score matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR] 0.29, 95% CI 0.06–1.38), CDI recurrence (HR 0.62, 95% CI 0.26–1.49), or failure (HR 0.50, 95% CI 0.23–1.07). Conclusion: Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger

Risk Factors Associated with Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case–control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93–33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20–19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03–7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8–128 mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58–25.33] and high-level (MIC ≥256 mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89–66.30) mupirocin resistance. To our knowledge, this is the first case–control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance

Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients

Study Objective: To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients. Design: Retrospective cohort study. Data Source: National Veterans Affairs standardized databases. Patients: A total of 263 obese and 71 extremely obese (actual body weight range 72–244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin-resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. Measurements and Main Results: Patients with steady-state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15–20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p Conclusion: In this real-world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight-based daily dose than obese patients to reach target vancomycin trough concentrations

Student nurses' experiences of discrimination and racism on work placements: What can higher education institutions do?

Background There is persistent interpersonal, institutional and structural racism within the health sector and higher education. Such anti-Black and anti-Brown racisms are experienced by nursing students, nursing apprentices and fully qualified nurses. This discrimination intersects with other characteristics, namely gender and student status, which can make the nursing profession an unsafe environment for many. Objectives To understand student nurses' experiences of racism and intersecting oppressions, at university and on work placement. Design A qualitative descriptive study with individual interviews and focus groups. Settings A widening participation higher education institution in London, UK. Participants Twenty-four student nurses and nurse apprentices studying on an adult nursing programme. Methods Students were recruited through purposive sampling. In-depth data relating to student nurses' perspectives and experiences were gathered through two focus groups and three individual interviews conducted by student nurse peers. Interviews were transcribed verbatim and open coding was used to analyse transcripts using comparison and thematic analysis. Results Three key themes arose: safety and support in the university space; hierarchical treatment in work placements due to intersecting race and ‘student’ identities, and; direct racism by patients and staff in work placements. Conclusions Student nurses expressed their vulnerability to discrimination and racism whilst on placement in the National Health Service. More opportunities within university curricula are needed for student nurses to learn about, reflect on, and gain support for managing experiences of discrimination in the health system

The Effects of Obesity on the Comparative Effectiveness of Linezolid and Vancomycin in Suspected Methicillin-Resistant \u3cem\u3eStaphylococcus aureus\u3c/em\u3e Pneumonia

Background: Methicillin-Resistant Staphylococcus aureus (MRSA) has become a leading cause of pneumonia in the United States and there is limited data on treatment outcomes in obese patients.We evaluated the effectiveness of linezolid compared to vancomycin for the treatment of MRSA pneumonia in a national cohort of obese Veterans. Methods: This retrospective cohort study included obese patients (body mass index ≥ 30) admitted to Veterans Affairs hospitals with MRSA-positive respiratory cultures and clinical signs of infection between 2002 and 2012. Patients initiating treatment with either vancomycin or linezolid, but not both, were selected for inclusion. Propensity matching and adjustment of Cox proportional hazards regression models quantified the effect of linezolid compared with vancomycin on time to hospital discharge, intensive care unit discharge, 30-day mortality, inpatient mortality, therapy discontinuation, therapy change, 30-day readmission, and 30-day MRSA reinfection. We performed sensitivity analyses by vancomycin Minimum Inhibitory Concentrations (MICs) and true trough levels. Results: We identified 101 linezolid and 2,565 vancomycin patients. Balance in baseline characteristics between the treatment groups was achieved within propensity score quintiles and between propensity matched pairs (76 pairs). No significant differences were observed for the outcomes assessed. Among patients with vancomycin MICs of ≤ 1 μg/mL, the linezolid group had a significantly lower mortality rate, increased length of hospital stay, and longer therapy duration. There were no differences between the linezolid and vancomycin MICs of ≥ 1.5 μg/ mL groups. Clinical outcomes among those with vancomycin trough concentrations of 15-20 mg/L were similar to patients treated with linezolid. Conclusions: In our real-world comparative effectiveness study among obese patients with suspected MRSA pneumonia, linezolid was associated with a significantly lower mortality rate as compared to the vancomycin-treated patients with lower vancomycin MICs. Further studies are needed to determine whether this beneficial effect is observed in other study populations

Comparative Effectiveness of Linezolid and Vancomycin Among a National Veterans Affairs Cohort with Methicillin-Resistant Staphylococcus aureus Pneumonia

Study Objective: As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real-world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Design: Retrospective cohort study. Data Source: Veterans Health Administration national databases. Patients: Adults admitted to Veterans Affairs hospitals between January 2002 and September 2010 with diagnosis codes for MRSA and pneumonia, and who initiated and received at least 3 days of continuous intravenous vancomycin therapy (4943 patients) or intravenous or oral linezolid therapy (328 patients) while in the hospital. Measurements and Main Results: Propensity score–adjusted Cox proportional hazards regression models quantified the effect of linezolid compared with vancomycin on time to 30-day mortality (primary outcome), therapy change, hospital discharge, discharge from intensive care, intubation, 30-day readmission, and 30-day MRSA reinfection. In addition, a composite outcome of clinical success was defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Subgroup analyses were performed in a validated microbiology-confirmed MRSA subgroup and clinical subgroup meeting clinical criteria for infection. Although a number of baseline variables differed significantly between the vancomycin and linezolid treatment groups, balance was achieved within propensity score quintiles. A significantly lower rate of therapy change was observed in the linezolid group (adjusted hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48–0.96). The clinical success rate was significantly higher among patients treated with linezolid (adjusted HR 1.25, 95% CI 1.07–1.47). Comparable findings were observed in the subgroup analyses. Conclusion: Individual clinical outcomes were similar among patients treated for MRSA pneumonia with linezolid compared with vancomycin. A significantly higher rate of the composite outcome of clinical success was observed, however, among patients treated with linezolid compared with vancomycin

Treatment, Clinical Outcomes, and Predictors of Mortality among a National Cohort of Admitted Patients with Acinetobacter baumannii Infection

The objectives were to analyze treatment, clinical outcomes, and predictors of mortality in hospitalized patients with Acinetobacter baumannii infection. This was a retrospective cohort study of inpatients with A. baumannii cultures and treatment from 2010 to 2019. Patients who died during admission were compared to those who survived, to identify predictors of inpatient mortality, using multivariable unconditional logistic regression models. We identified 4,599 inpatients with A. baumannii infection; 13.6% died during admission. Fluoroquinolones (26.8%), piperacillin-tazobactam (24%), and carbapenems (15.6%) were used for treatment. Tigecycline (3%) and polymyxins (3.7%) were not used often. Predictors of inpatient mortality included current acute respiratory failure (adjusted odds ratio [aOR] 3.94), shock (aOR 3.05), and acute renal failure (aOR 2.01); blood (aOR 1.94) and respiratory (aOR 1.64) infectious source; multidrug-resistant A. baumannii (MDRAB) infection (aOR 1.66); liver disease (aOR 2.15); and inadequate initial treatment (aOR 1.30). Inpatient mortality was higher in those with MDRAB versus non-MDRAB (aOR 1.61) and in those with CRAB versus non-CRAB infection (aOR 1.68). Length of stay \u3e10 days was higher among those with MDRAB versus non-MDRAB (aOR 1.25) and in those with CRAB versus non-CRAB infection (aOR 1.31). In our national cohort of inpatients with A. baumannii infection, clinical outcomes were worse among those with MDRAB and/or CRAB infection. Predictors of inpatient mortality included several current conditions associated with severity, infectious source, underlying illness, and inappropriate treatment. Our study may assist health care providers in the early identification of admitted patients with A. baumannii infection who are at higher risk of death

Predictors of Mortality Among U.S. Veterans With \u3cem\u3eStreptococcus Pneumoniae\u3c/em\u3e Infections

Introduction Serious Streptococcus pneumoniae infections, encompassing pneumonia, bacteremia, and meningitis, are a major cause of mortality. However, literature regarding mortality is often limited to invasive pneumococcal disease, excluding pneumonia. This study sought to identify predictors of mortality among adults with serious pneumococcal disease, including pneumonia and invasive pneumococcal disease. Methods This was a nested case-control study of unvaccinated older Veterans with positive S. pneumoniae cultures (blood, cerebrospinal fluid, respiratory) admitted to Veterans Affairs medical centers nationally between 2002 and 2011. Patients vaccinated against pneumococcal disease were excluded. Using multivariable logistic regression, predictors of 30-day mortality were identified, including patient demographics, comorbidities during admission, and medical history within the previous year. Results Among 9,468 patients, there were 9,730 serious pneumococcal infections; 1,764 (18.6%) resulted in death within 30 days (cases), whereas 7,966 did not (controls). Pneumonia accounted for half (49.4%, n=871) of all deaths. Mortality predictors consistent with vaccine recommendations included dialysis (during hospitalization, OR=3.35, 95% CI=2.37, 4.72), moderate to severe liver disease (during hospitalization, OR=2.47, 95% CI=1.53, 3.99; within 1 year, OR=1.49, 95% CI=1.01, 2.20), and neutropenia (during hospitalization, OR=2.67, 95% CI=1.32, 5.42). Predictors not included in current recommendations included dementia (during hospitalization, OR=1.8, 95% CI=1.23, 2.61) and neurologic disorders (during hospitalization, OR=1.86, 95% CI=1.42, 2.45; within 1 year, OR=1.28, 95% CI=1.02, 1.59). Conclusions Several mortality predictors among unvaccinated Veterans with serious pneumococcal disease were consistent with pneumococcal vaccine recommendations, including organ or immune system dysfunction–related conditions. Other predictors, including neurologic disorders or dementia, may warrant expanded vaccination recommendations

Risk stacking of pneumococcal vaccination indications increases mortality in unvaccinated adults with Streptococcus pneumoniae infections

Background Several chronic disease states have been identified as pneumococcal vaccination indications due to their ability to increase pneumococcal disease development and subsequent mortality. However, the risk of mortality according to the number of these disease states present is unknown. We sought to determine the impact of concomitant, multiple risk factors (stacked risks) for pneumococcal disease on 30-day mortality in adults. Methods This was a national case-control study of unvaccinated older Veterans (≥50 years of age) admitted to Veterans Affairs medical centers from 2002 to 2011 with serious pneumococcal infections (pneumonia, bacteremia, meningitis) based on positive S. pneumoniae blood, cerebrospinal fluid, or respiratory cultures, respectively. Cases were those not alive 30 days following culture, while controls were alive. Using logistic regression, we quantified risk of 30-day mortality among patients with stacked risk factors, including age ≥65 years, alcohol abuse, chronic heart disease, chronic liver disease, chronic respiratory disease, diabetes mellitus, immunodeficiency, and smoking. Results We identified 9730 serious pneumococcal infections, with an overall 30-day mortality rate of 18.6% (1764 cases, 7966 controls). Infection types included pneumonia (62%), bacteremia (26%), and bacteremic pneumonia (11%). Along with eight individual risk factors, we assessed 247 combinations of risk factors. Most cases (85%) and controls (74%) had at least two risk factors. Mortality increased as risks were stacked, up to six risk factors (one: OR 1.5, CI 1.08–2.07; two: OR 2.01, CI 1.47–2.75; three: OR 2.71, CI 1.99–3.69; four: OR 3.27, CI 2.39–4.47; five: OR 3.63, CI 2.60–5.07; six: OR 4.23, CI 2.69–6.65), with each additional risk factor increasing mortality an average of 55% (±13%). Conclusions Among adults ≥50 years with serious pneumococcal disease, mortality risk increased approximately 55% as vaccination indications present increased. Mortality with six stacked indications was double that of two indications

Predictors of Clinical Success Among a National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus aureus Pneumonia

Background: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions. Objectives: We sought to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of MRSA pneumonia patients. Methods: A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Controls represented non-success, defined as therapy change, intubation, ICU admission, re-admission, or death between treatment initiation and day 14. The potential predictors assessed included treatment, patient demographics and admission characteristics, previous healthcare and medication exposures, comorbidities, and medical history. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression. Results: Our study included 2442 cases of clinical success and 1290 controls. Demographics varied between the clinical success and non-success groups, including age, race, and region of facility. A current diagnosis of chronic respiratory disease (46% vs 42%) and diagnosis of pneumonia in the year prior to the MRSA pneumonia admission (37% vs 32%) were both more common in the clinical success group. Despite these significant differences, only two predictors of clinical success were identified in our study: previous complication of an implant or graft, including mechanical complications and infections, in the year prior to the MRSA pneumonia admission (OR, 1.55; 95% CI, 1.17–2.06) and treatment with linezolid (1.53; 1.12–2.10). Predictors of non-success included concomitant urinary tract infection diagnosis (OR, 0.82; 95% CI, 0.70–0.96), intravenous line (0.76; 0.66–0.89), previous coagulopathy (0.74; 0.56–0.96), previous amputation procedure (0.72; 0.53–0.98), current coagulopathy diagnosis (0.71; 0.53–0.96), dialysis (0.54; 0.38–0.76), multiple inpatient procedures (0.53; 0.45–0.62), inpatient surgery (0.48; 0.41–0.57), and previous endocarditis (0.24; 0.07–0.81). Discussion: MRSA pneumonia tends to affect complex patients, and identification of the predictors of clinical success is useful when considering different therapeutic approaches. Conclusions: In a national cohort of VA patients with MRSA pneumonia, treatment was the only modifiable variable predicting clinical success