Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis.

BACKGROUND: This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies. METHODS: A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence. RESULTS: Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23-.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27-.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46-.99]). CONCLUSIONS: AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.

Understanding the Components, Calculation, and Impact of Monthly and Seasonal Variation of the Standardized Antimicrobial Utilization Ratio (SAAR).

This study sought to characterize the impact of 3 types of variation on the Standardized Antimicrobial Administration Ratio (SAAR) utilizing local National Healthcare Safety Network (NHSN) data. SAAR and antimicrobial days per 1,000 days present (AD/1000DP) were compiled monthly for Northwestern Memorial Hospital from 2014 to 2016. Antimicrobial consumption was aggregated into agent categories (via NHSN criteria). Month-to-month changes in SAAR and AD/1000DP were evaluated. Azithromycin and oseltamivir AD/1000DP from 2012 through 2017 were explored for seasonal variation. A sensitivity analysis was performed to explore the effect of seasonality and altered consumption at other hypothetical hospitals on the SAAR. Across agent categories for both the intensive care unit (n = 4) and general wards (n = 4), the average matched-month percent change in AD/1000DP was correlated with the corresponding change in SAAR (coefficient of determination of 0.99). The monthly mean ± standard deviation (SD) AD/1000DP was 235 (range, 47.2 to 661.5), and the mean ± SD SAAR was 1.09 ± 0.26 (range, 0.79 to 1.09) across the NHSN agent categories. Five seasons exhibited seasonal variation in AD/1000DP for azithromycin with a mean percent change of 26.76% (range, 22.27 to 30.69). Eight seasons exhibited seasonal variation in AD/1000DP for oseltamivir with a mean percent change of 129.1% (range, 32.01 to 352.74). The sensitivity analyses confirm that antimicrobial usage at comparator hospitals does not impact the local SAAR, and seasonal variation of antibiotics has the potential to impact SAAR. Month-to-month changes in the SAAR mirror monthly changes in an institution's AD/1000DP. Seasonal variation is an important variable for future SAAR consideration, and the variable antibiotic use at peer hospitals is not currently captured by the SAAR methodology.

Measuring the impact of varying denominator definitions on standardized antibiotic consumption rates: implications for antimicrobial stewardship programmes.

Objectives: To quantify the impact of varying the at-risk days definition on the overall report of at-risk days and on the calculated standardized consumption rates (SCRs) for piperacillin/tazobactam, amikacin, daptomycin and vancomycin. Methods: Data were evaluated for two system hospitals, an 894 bed academic centre and a 114 bed community hospital. Aggregate inpatient antibiotic administration and occupancy data were extracted from electronic databases at the facility-wide level. Occupancy data were reported from admission-discharge-transfer systems. At-risk days were defined as hospital days present (DP), patient days (PD), persons present (PP) and billing days (BD). Inpatient antimicrobial days of therapy (DOT) across four major antimicrobial agents were used to calculate facility-wide SCRs using each denominator and were evaluated by least-squares regression and R2 values. Results: Within the 894 bed academic hospital, the average monthly facility-wide days were 28 424, 22 198, 15 957 and 14 789 by the DP, PP, PD and BD definitions, respectively. Within the 114 bed community hospital, the average monthly facility-wide days were 5175, 3523 and 2816 by the DP, PP and PD definitions, respectively. Strong concordance was observed between facility-wide SCRs using the DP and PP definitions in both the academic (R2 = 0.99, y = 0.78x - 0.001) and community (R2 = 0.99, y = 0.68x - 0.03) centres across all four inpatient antibiotics evaluated. In an analysis of piperacillin/tazobactam SCRs, rates were over-predicted by 28%-93% at the facility-wide level across centres using alternative denominators. Conclusions: We found that data source and definitions of at-risk denominator days meaningfully impact antibiotic SCRs. Centres should carefully consider these potential sources of variation when setting consumption benchmarks and internally evaluating use.

Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

OBJECTIVES: Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. METHODS: This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. RESULTS: We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P < 0.01), more often male (72.2% versus 36.1%, P=0.02) and more likely to be African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ±â€ŠSD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ±â€Š1.5 mg, P < 0.01), but not ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ±â€Š1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. CONCLUSIONS: The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.

Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti-infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because many of the shortages stem from problems with manufacturing and distribution, federal legislation has been introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti-infective shortages in the United States and explore the reasons for inadequate drug supply.

Evaluation of clinical outcomes in patients with bloodstream infections due to Gram-negative bacteria according to carbapenem MIC stratification.

Predictive modeling suggests that actual carbapenem MIC results are more predictive of clinical patient outcomes than categorical classification of the MIC as susceptible, intermediate, or resistant. Some have speculated that current CLSI guidelines' suggested thresholds are too high and that clinical success is more likely if the MIC value is ≤1 mg/liter for certain organisms. Patients treated with carbapenems and with positive blood cultures for Pseudomonas aeruginosa, Acinetobacter baumannii, or extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria were considered for evaluation in this clinical retrospective cohort study. Relevant patient demographics and microbiologic variables were collected, including carbapenem MIC. The primary objective was to define a risk-adjusted all-cause hospital mortality breakpoint for carbapenem MICs. Secondarily, we sought to determine if a similar breakpoint existed for indirect outcomes (e.g., time to mortality and length of stay [LOS] postinfection for survivors). Seventy-one patients met the criteria for study inclusion. Overall, 52 patients survived, and 19 died. Classification and regression tree (CART) analysis determined a split of organism MIC between 2 and 4 mg/liter and predicted differences in mortality (16.1% versus 76.9%; P < 0.01). Logistic regression controlling for confounders identified each imipenem MIC doubling dilution as increasing the probability of death 2-fold (adjusted odds ratio [aOR] 2.0; 95% confidence interval [CI], 1.3 to 3.2). Secondary outcomes were similar between groups. This study revealed that patients with organisms that had a MIC of ≥4 mg/liter had worse outcomes than patients whose isolates had a MIC of ≤2 mg/liter, even after adjustment for confounding variables. We recommend additional clinical studies to better understand the susceptibility breakpoint for carbapenems.

Successful treatment of extensively drug-resistant Acinetobacter baumannii peritoneal dialysis peritonitis with intraperitoneal polymyxin B and ampicillin-sulbactam.

OBJECTIVE: To describe a case of extensively drug-resistant (XDR) Acinetobacter baumannii peritoneal dialysis (PD)-associated peritonitis successfully treated with combination antibiotics, including intraperitoneal polymyxin B, with retention of the catheter. CASE SUMMARY: A 54-year-old woman with end-stage renal disease receiving chronic PD and recent antibiotic and hospital exposure presented with abdominal pain, nausea, and vomiting. She was found to have XDR A. baumannii PD peritonitis. Treatment was initiated with intravenous and intraperitoneal ampicillin-sulbactam, followed by the addition of intraperitoneal polymyxin B based on susceptibilities. The patient recovered without the need for catheter removal or switch to hemodialysis. DISCUSSION: The frequency of XDR A. baumannii as a nosocomial pathogen is increasing, and polymyxins are being used more often as part of combination therapy for infections caused by this organism. Neither XDR A. baumannii PD peritonitis nor the use of intraperitoneal polymyxin B has been well described. In our patient, intraperitoneal dosing of polymyxin B was determined based on limited published pharmacokinetic and pharmacodynamic data. CONCLUSIONS: A case of XDR A. baumannii PD peritonitis was successfully treated with combination antibiotic therapy, including intraperitoneal polymyxin B, without major complications.

Decreasing incidence of Acinetobacter baumannii pneumonia and trends in antibiotic consumption: A single-center retrospective observational study.

OBJECTIVE: To describe the epidemiology of Acinetobacter baumannnii (AB) pneumonia at our center, including the antibiotic exposure patterns of individual AB pneumonia cases and to investigate whether hospital-wide antibiotic consumption trends were associated with trends in AB pneumonia incidence. DESIGN: Single-center retrospective study with case-control and ecological components. SETTING: US private tertiary-care hospital. PARTICIPANTS AND METHODS: All hospitalized patients with AB infection from 2008 to 2019 were identified through laboratory records; for those with AB pneumonia, medical records were queried for detailed characteristics and antibiotic exposures in the 30 days preceding pneumonia diagnosis. Hospital-wide antibiotic consumption data from 2015 through 2019 were obtained through pharmacy records. RESULTS: Incidence of both pneumonia and nonrespiratory AB infections decreased from 2008 to 2019. Among the 175 patients with AB pneumonia, the most frequent antibiotic exposure was vancomycin (101 patients). During the 2015-2019 period when hospital-wide antibiotic consumption data were available, carbapenem consumption increased, and trends negatively correlated with those of AB pneumonia (r = -0.48; P = .031) and AB infection at any site (r = -0.63; P = .003). Conversely, the decline in AB infection at any site correlated positively with concurrent declines in vancomycin (r = 0.55; P = .012) and quinolone consumption (r = 0.51; P = .022). CONCLUSIONS: We observed decreasing incidence of AB infection despite concurrently increasing carbapenem consumption, possibly associated with declining vancomycin and quinolone consumption. Future research should evaluate a potential role for glycopeptide and quinolone exposure in the pathogenesis of AB infection.

Impact of early antimicrobial stewardship intervention in patients with positive blood cultures: results from a randomized comparative study.

BACKGROUND: Antimicrobial stewardship intervention (ASI) appears to be necessary to realize the full benefits of rapid diagnostic technologies in clinical practice. This study aimed to compare clinical outcomes between early ASI paired with matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) compared with MALDI-TOF with standard of care (SOC) reporting in patients with positive blood cultures. METHODS: Adult patients with positive blood cultures and organism speciation via MALDI-TOF admitted between February 2015 and September 2015 were randomized to ASI or SOC in a 1:1 fashion. Patients admitted for at least 48 h following positive culture were included in analyses. ASI was defined as a clinical assessment by a stewardship team member with non-binding treatment recommendations offered to the primary team. The primary outcome was time to definitive therapy. Secondary outcomes included post-culture length of stay (LOS), time to first change in antibiotics, and in-hospital mortality. RESULTS: In total, 149 patients were included in the analyses (76 in the ASI group and 73 in the SOC group). ASI and SOC arms did not differ according to age, sex, comorbidities or severity of illness. Gram-positive organisms were common in both SOC and ASI arms (74.0 vs. 61.8%, P=0.11). Time to definitive therapy was reduced, on average, by 30.3 h in the ASI group (71.6 vs. 41.3 h, P=0.01). Hospital LOS following the first positive blood culture was significantly shorter in the ASI group (8.7 vs. 11.2 days, P=0.049). CONCLUSIONS: ASI combined with MALDI-TOF reduced the time to definitive therapy and time to first change in antibiotics, and was associated with a shorter post-culture LOS.

Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections.

Nosocomial Acinetobacter baumannii bloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance in A. baumannii and patient outcomes remains unclear. A retrospective cohort study was conducted on patients with A. baumannii bacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistant A. baumannii (CNRAB) and carbapenem-resistant A. baumannii (CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P < 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P = 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5; P < 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%; P = 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P = 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

Low incidence of renal impairment observed in tenofovir-treated patients.

OBJECTIVES: To compare the incidence of renal impairment in HIV-infected patients exposed versus unexposed to tenofovir and to characterize risk factors associated with renal impairment. METHODS: We undertook a retrospective cohort and nested case-control study of 514 Northwestern University HIV Outpatient Study participants who received antiretroviral therapy (ART) between 1 August 2001 and 31 July 2007. Renal impairment was defined as meeting at least one of two validated criteria based on serum creatinine, calculated glomerular filtration rate and creatinine clearance. Multivariable analysis was performed to identify risk factors for renal impairment. RESULTS: Renal impairment occurred in 14% (n = 72) of the cohort and was not correlated with exposure to tenofovir in univariate analyses. In multivariable analysis, more advanced age [odds ratio (OR) = 1.04, P = 0.02], diabetes (OR = 3.6, P < 0.01), decreased weight (OR = 0.97, P = 0.02) and endpoint CD4 ≤200 cells/mm(3) (OR = 2.5, P = 0.03) were positive predictors of renal impairment; tenofovir exposure (OR = 0.41, P = 0.01) was negatively correlated with renal impairment. CONCLUSIONS: Tenofovir-containing ART was associated with less renal impairment than ART without tenofovir in a patient cohort with a high incidence of renal impairment. Chronic co-morbid conditions known to be associated with renal impairment should be excluded prior to attributing renal impairment to tenofovir.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort.

BACKGROUND: The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. METHODS: This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. RESULTS: One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001). CONCLUSIONS: Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.

Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19.

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

Effect of differences in MIC values on clinical outcomes in patients with bloodstream infections caused by gram-negative organisms treated with levofloxacin.

Emerging evidence suggests that current fluoroquinolone dosing strategies may be inadequate to treat bloodstream infections caused by organisms classified as sensitive. This study sought to determine if differences in MICs for levofloxacin-susceptible gram-negative organisms correlate with differences in patient outcomes. A retrospective cohort study evaluated patients treated with levofloxacin for bloodstream infections caused by susceptible gram-negative organisms. Patients infected with gram-negative organisms for which MICs indicated susceptibility were categorized into three groups: those with organisms for which MICs were low (

Diagnostic stewardship of C. difficile testing: a quasi-experimental antimicrobial stewardship study.

OBJECTIVE: We evaluated whether a diagnostic stewardship initiative consisting of ASP preauthorization paired with education could reduce false-positive hospital-onset (HO) Clostridioides difficile infection (CDI). DESIGN: Single center, quasi-experimental study. SETTING: Tertiary academic medical center in Chicago, Illinois. PATIENTS: Adult inpatients were included in the intervention if they were admitted between October 1, 2016, and April 30, 2018, and were eligible for C. difficile preauthorization review. Patients admitted to the stem cell transplant (SCT) unit were not included in the intervention and were therefore considered a contemporaneous noninterventional control group. INTERVENTION: The intervention consisted of requiring prescriber attestation that diarrhea has met CDI clinical criteria, ASP preauthorization, and verbal clinician feedback. Data were compared 33 months before and 19 months after implementation. Facility-wide HO-CDI incidence rates (IR) per 10,000 patient days (PD) and standardized infection ratios (SIR) were extracted from hospital infection prevention reports. RESULTS: During the entire 52 month period, the mean facility-wide HO-CDI-IR was 7.8 per 10,000 PD and the SIR was 0.9 overall. The mean ± SD HO-CDI-IR (8.5 ± 2.0 vs 6.5 ± 2.3; P < .001) and SIR (0.97 ± 0.23 vs 0.78 ± 0.26; P = .015) decreased from baseline during the intervention. Segmented regression models identified significant decreases in HO-CDI-IR (Pstep = .06; Ptrend = .008) and SIR (Pstep = .1; Ptrend = .017) trends concurrent with decreases in oral vancomycin (Pstep < .001; Ptrend < .001). HO-CDI-IR within a noninterventional control unit did not change (Pstep = .125; Ptrend = .115). CONCLUSIONS: A multidisciplinary, multifaceted intervention leveraging clinician education and feedback reduced the HO-CDI-IR and the SIR in select populations. Institutions may consider interventions like ours to reduce false-positive C. difficile NAAT tests.

Increasing incidence of linezolid-intermediate or -resistant, vancomycin-resistant Enterococcus faecium strains parallels increasing linezolid consumption.

Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r(2) = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual.

OBJECTIVE: To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient. CASE SUMMARY: A 39-year-old morbidly obese (weight 167 kg, body mass index 50 kg/m2) man was treated with piperacillin/tazobactam 3.375 g every 4 hours for recurrent cellulitis. The wound culture grew Groups A and B Streptococcus and rare Pseudomonas aeruginosa. Blood samples were obtained at steady-state from a peripheral venous catheter at 0, 0.5, 1, 2, 3, and 4 hours after the start of the infusion. Population pharmacokinetics were generated from a previously published data set. The serum concentrations of piperacillin/tazobactam obtained in the patient were compared with the 95% confidence interval from the representative population. Pharmacokinetic parameters such as maximal serum concentration, minimal serum concentration, average steady-state concentration, half-life, elimination rate constant, volume of distribution (V(d)), clearance, area under the curve at steadystate, and percent of time greater than the minimum inhibitory concentration (%t>MIC) were calculated and qualitatively compared between the sample and the population. DISCUSSION: Substantial differences were noted in both the absolute values at the times of sample collection and the overall concentration-versus-time profile of both compounds. The morbidly obese individual compared with the population demonstrated a reduced average serum steady-state concentration: 39.8 mg/L versus 123.6 mg/L, an increased V(d): 54.3 L versus 12.7 L, and an increased half-life: 1.4 hours versus 0.6 hours, respectively. The %t >MIC of piperacillin for the patient, assuming MICs of 2, 4, 8, 16, 32, 64, and 128 mg/L, was 100%, 100%, 90.9%, 55.4%, 19.9%, 0%, and 0%, respectively. CONCLUSIONS: Pathogens with elevated MICs may require altered dosing schemes with piperacillin/tazobactam. Future studies are warranted to assess increased dosages, more frequent dosing intervals, or continuous infusion dosing schemes for obese individuals with serious infections.

Implementation of a cefazolin-based stewardship pathway for methicillin-susceptible Staphylococcus aureus bloodstream infections paired with infectious diseases consultation.

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolin's lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA.

The clinical impact of linezolid susceptibility reporting in patients with vancomycin-resistant enterococci.

Linezolid remains a mainstay of therapy for vancomycin-resistant enterococci (VREs), but resistance has emerged. We describe a cohort of 20 patients with linezolid-intermediate or resistant VRE (LIRVRE) reported by Etest and disk diffusion testing, 18 of whom demonstrated linezolid susceptibility by agar dilution on further investigation. Patients with reported LIRVRE were matched based on culture site and enterococcal species to patients with linezolid-susceptible VRE (LSVRE) in a 1:3 ratio. Patients with reported LIRVRE developed more nosocomial infections (P = .04), had more central lines placed (P = .04), and underwent more computed tomography scans related to VRE infection (P = .02). Multivariate analysis revealed increased surgical procedures related to VRE infections (P = .008), increased linezolid use during hospital stay (P = .03), and delayed culture and susceptibility results compared with those with LSVRE (P = .006). Therefore, inaccurate detection and reporting of LIRVRE by disk diffusion and Etest is associated with increased patient morbidity and resource use.