New method and lower dosing of vancomycin could treat MRSA with reduced AKI
Lower doses of vancomycin may successfully treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while reducing risk of acute kidney injury (AKI), a recent study found.
The prospective observational study included 265 adults with MRSA bacteremia from 14 hospitals. The patients were divided by whether they achieved area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds of vancomycin of at least 650 by broth microdilution or 320 by Etest. These thresholds have been previously associated with lower incidence of treatment failure, which the study defined as mortality within 30 days or persistent bacteremia at seven days. Results were published by Clinical Infectious Diseases on June 3, 2019.
Treatment failure occurred in 18% of patients; 26% developed AKI. Patients who achieved the vancomycin thresholds did not have lower rates of treatment failure, and the study was not able to identify a threshold associated with lower risk of treatment failure. Higher AUC on day 2 was associated with AKI risk. Patients with an AUC of 515 or less had the greatest likelihood of avoiding both treatment failure and AKI, leading the authors to conclude that this value should be a target for vancomycin dosing in such patients. They noted that few patients in the study had AUCs below 400, so they weren't able to find a lower bound on the therapeutic range.
“These results have important implications for clinical practice. Clinicians and guideline authors should reassess the balance of benefits and risks of targeting higher AUC/MIC for patients with MRSA bacteremia,” the authors said. “The findings also suggest that vancomycin dosing should be guided by the AUC instead of the AUC/MIC ratio.” They noted that issues with MIC include the narrow range of MIC values among contemporary MRSA isolates, the imprecision of MIC measurement, the variability of testing methods, and the delay until values are available.
The study was limited by the factors inherent in observational research, the authors noted. It also only included adult, non-neutropenic, nondialysis patients, and nearly all MRSA isolates in the study had vancomycin MICs under 2 mg/L.
An accompanying editorial noted that most medical centers report not being ready yet to change from trough-based dosing of vancomycin to AUC-based dosing, but more literature and guidelines on the topic might lead them to consider adding it to practice. “This study, along with several other recent publications, suggest that an AUC range between 400 to 600 μg×h/mL was most commonly linked to clinical success, whereas an increased risk for vancomycin-associated acute kidney injury or nephrotoxicity occurs when an AUC threshold exceeds a range of 600 to 800 μg×h/mL,” the editorialist said.
Fluid overload associated with adverse event risk in critically ill AKI patients
Fluid overload may increase risk for major adverse kidney events in critically ill patients who require continuous renal replacement therapy (CRRT) for acute kidney injury (AKI), a recent study found.
Researchers conducted a retrospective cohort study at a single ICU at a tertiary medical center in Kentucky to determine how fluid overload affected adverse event risk in this patient population. They assessed fluid overload as fluid balance from admission to initiation of CRRT, adjusted for body weight, and defined major adverse kidney events as a composite of death, dependence on renal replacement therapy, or, in patients not on renal replacement therapy, inability to recover 50% of baseline estimated glomerular filtration rate up to 90 days after discharge. The study results were published June 3, 2019, by Critical Care Medicine and appeared in the September 2019 issue.
Four hundred eighty-one patients were included in the study. The mean age was 56 years, and most (64.4%) were men. Two hundred forty-three patients (50.5%) had fluid overload less than or equal to 10% when CRRT was initiated, and 238 patients (49.5%) had fluid overload above 10%. Those with fluid overload less than or equal to 10% were less likely to have major adverse kidney events than those with fluid overload greater than 10% (71.6% vs. 79.4%; P=0.047). In multivariable logistic regression analysis, fluid overload above 10% was seen to be associated with 58% higher odds of major adverse kidney events. This finding continued to be seen after adjustment for timing of CRRT initiation. Every one-day increase in time from ICU admission to initiation of CRRT was associated with a 2.7% increased odds of major adverse kidney events. Fluid overload greater than 10% was independently associated with 82% increased odds of hospital mortality (P=0.004) and 2.5 fewer ventilator-free days (P=0.044) versus fluid overload of 10% or lower.
The researchers noted that their results were vulnerable to selection bias and may not be generalizable to other critically ill populations, among other limitations. They concluded that in critically ill patients with AKI who require CRRT, fluid overload above 10% was independently associated with increased risk of major adverse kidney events. Clinicians should routinely calculate fluid overload in the critical care setting to prevent it and its potential consequences, the authors recommended. They also noted that an association was seen between major adverse kidney outcomes and increased time from ICU admission to CRRT initiation. “Further randomized controlled trials are needed to determine how conservative fluid management strategies, including diuretic use and early initiation of CRRT for volume removal, will affect short- and long-term renal outcomes,” they wrote.
Sepsis improvement program widened disparities between white and black patients
An initiative to improve sepsis response in New York State improved care overall but was associated with widened disparities in care between white and black patients, a recent study found.
The retrospective study included 50,029 ED encounters for severe sepsis or septic shock in New York State hospitals from April 1, 2014, to June 30, 2016. A 2013 state regulation required all nonfederal hospitals in New York to report in-hospital mortality and initiation and implementation of three- and six-hour protocols for the early detection and treatment of sepsis or septic shock. Results were published in the July 2019 Health Affairs.
The studied patients were 66.6% white, 17.3% black, 11.0% Hispanic, and 5.1% Asian. Black, Hispanic, and Asian patients were more likely than white patients to receive care at hospitals with more certified beds, teaching hospitals, and locations in New York City. In the first quarter of the studied period, there were no significant differences in unadjusted rates of three-hour protocol completion by racial group: white (60.8%), black (59.7%), Hispanic (62.6%), and Asian (58.8%). However, during follow-up, rates of three-hour protocol completion increased by 14.0 percentage points among white patients compared to 5.3 percentage points among black patients.
Improvements were 6.7 and 8.4 percentage points for Hispanic and Asian patients, respectively, but that did not represent a significant difference from the other groups. White patients also experienced greater improvement in six-hour protocol completion than black patients (14.7 vs. 6.8 percentage points).
Sensitivity analyses showed that the disparity in use of three-hour protocols between white and black patients existed irrespective of where sepsis was first diagnosed (ED, ICU, or ward). However, the disparities were not found between patients of the two races treated in the same hospitals. Instead, the study found the disparities could be attributed to an inverse relationship in which hospitals with a higher proportion of black sepsis patients showed less improvement in use of the three-hour protocol.
“Our study suggests an urgent need to understand why improvements in sepsis care lagged in hospitals in New York that care for higher proportions of minority patients,” said the study authors. The findings also “raise concerns about the potential for broadly targeted quality improvement initiatives to exacerbate inequities in care,” they added. They noted that possible explanations for the findings include previous observations that minority-serving hospitals have fewer resources, less quality improvement infrastructure, more ED overcrowding, and worse nurse-to-patient ratios. The authors called for stratified reporting on quality improvement initiatives, attention to the potential negative effects of related financial incentives on minority-serving hospitals, and investigation into the causes of these disparities in order to potentially undertake efforts to remedy them.
Drug-resistance score helped guide antibiotic use in ED patients with pneumonia
A prediction score integrated into an electronic clinical decision support tool reduced initial empiric broad-spectrum antibiotic use without increasing inadequate empiric antibiotic therapy or mortality in patients presenting to the ED with pneumonia, a recent study found.
Researchers conducted a quasi-experimental, pre-post implementation study of the Drug Resistance in Pneumonia (DRIP) score, a previously validated prediction tool based on host risk factors. The decision support tool was programmed to calculate DRIP scores in real time through an automated query of the electronic health record for 10 criteria, which included risk factors such as antibiotic use in the previous 60 days and residence in a long-term care facility.
At four U.S. hospitals, the researchers compared effects of DRIP, which was integrated into the tool in 2015, with that of health care-associated pneumonia (HCAP) logic, used by the tool in 2012, for ED patients with pneumonia. The researchers estimated the score's effect on broad-spectrum antibiotic use within 12 hours of ED presentation (the primary outcome), mortality, hospital stay, and cost, adjusting for patient-level confounders. In addition, a recommendation was added to the tool advising clinicians to order a nasal swab for methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction testing in patients with high DRIP scores to aid in de-escalation of empiric vancomycin. Results were published online on May 8, 2019, by CHEST and appeared in the November 2019 issue.
A total of 2,169 adult admissions were analyzed, 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015. Broad-spectrum antibiotic use was about 10-fold higher than the incidence of drug-resistant pathogens. A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 compared to 33.0% in 2015 (P<0.001). Days of vancomycin therapy per 1,000 patient-days in 2012 were 287.3 compared to 238.8 in 2015 (P<0.001). Inadequate initial empiric antibiotics were prescribed in 1.1% of patients in 2012, compared to 0.5% in 2015 (P=0.12). Patients treated using the DRIP had a significant reduction in broad-spectrum antibiotic use (treatment effect odds ratio, 0.62 [95% CI, 0.39 to 0.98]; P=0.039). However, the average effects of the score on mortality, length of stay, and cost were not significant.
The study authors predicted that empiric broad-spectrum antibiotic use would be 18.9% after the stewardship intervention, which was lower than the actual results, suggesting that “the reduction would be greater had clinicians followed the tool recommendations explicitly,” they wrote. Confounding by indication was the primary limitation of the study, and further evaluation of the score in other EDs with varying patient demographics and resistance patterns is warranted, they noted.
“Compared to HCAP criteria, the DRIP score is a more effective tool to assist clinicians in accurately identifying the risk of drug-resistant pathogens in pneumonia,” the authors concluded. “Nevertheless, significant opportunities for improvement remain to reduce unnecessary antibiotic use in pneumonia.” They plan to reassess broad-spectrum antibiotic use three years after DRIP deployment, with the hypothesis that they will detect further reductions after clinicians become more familiar with the score and MRSA nasal swab strategies.