Overconsumption of Antibiotics

We applaud Thomas Van Boeckel and colleagues1 for their large analysis of antibiotic consumption in 71 countries. A 36% increase in use of antibiotics worldwide, 76% of which was in Brazil, Russia, India, China, and South Africa, is a concerning finding. In Europe and the USA, practitioners are increasingly aware of the importance of infection control and antimicrobial stewardship. However, 50% of antimicrobials, irrespective of setting, are used inappropriately.2,3 We agree that most increases in global antibiotic consumption are probably caused by inappropriate use and that coordinated efforts to improve antimicrobial use internationally are desperately needed

Simulating quantum correlations as a distributed sampling problem

It is known that quantum correlations exhibited by a maximally entangled qubit pair can be simulated with the help of shared randomness, supplemented with additional resources, such as communication, post-selection or non-local boxes. For instance, in the case of projective measurements, it is possible to solve this problem with protocols using one bit of communication or making one use of a non-local box. We show that this problem reduces to a distributed sampling problem. We give a new method to obtain samples from a biased distribution, starting with shared random variables following a uniform distribution, and use it to build distributed sampling protocols. This approach allows us to derive, in a simpler and unified way, many existing protocols for projective measurements, and extend them to positive operator value measurements. Moreover, this approach naturally leads to a local hidden variable model for Werner states.Comment: 13 pages, 2 figure

Simulation of bipartite qudit correlations

We present a protocol to simulate the quantum correlations of an arbitrary bipartite state, when the parties perform a measurement according to two traceless binary observables. We show that $\log(d)$ bits of classical communication is enough on average, where $d$ is the dimension of both systems. To obtain this result, we use the sampling approach for simulating the quantum correlations. We discuss how to use this method in the case of qudits.Comment: 7 page

Antimicrobial Stewardship Program Prompts Increased and Earlier Infectious Diseases Consultation

A recent analysis demonstrated that infectious diseases (ID) specialty intervention was associated with decreased mortality and hospital readmission. These benefits were greatest if involvement occurred within two days of hospital admission. Antimicrobial stewardship programs should augment the services of an ID specialist team and promote formal consultation. Implementation of an antimicrobial stewardship program at the Providence Veterans Affairs Medical Center was associated with an increased number of consults (increase of 72.2%) and decreased time to consult (3.5 days sooner), which might also dramatically improve patient outcomes, including mortality and readmission rates

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

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

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

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

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

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