Fecal transplants, contrast, and more

Summaries from ACP Hospitalist Weekly.

C. diff-related bloodstream infection seen less often with FMT vs. antibiotics

Treatment with fecal microbiota transplantation (FMT) rather than antibiotics for recurrent Clostridioides difficile infection was associated with a lower incidence of primary bloodstream infection, a prospective cohort study found.

Researchers enrolled 290 patients who were hospitalized from July 2013 to May 2018 with recurrent C. difficile infection at an academic medical center in Italy. Eligible patients were adults who had their first observable episode of recurrent C. difficile infection at the hospital and did not develop a secondary bloodstream infection from a known source. The primary outcome was the incidence of primary bloodstream infection within 90 days. Secondary outcomes were length of hospitalization and overall survival at 90 days. Results were published on Nov. 5, 2019, by Annals of Internal Medicine and appeared in the Nov. 19, 2019, issue.

The prospective study looked at 109 patients treated with FMT and 181 treated with antibiotics. Five of the FMT patients and 40 patients on antibiotics developed bloodstream infections. Due to differences between groups in many baseline characteristics, the researchers performed comparative analyses in a propensity-matched cohort (57 patients per treatment). Risk for bloodstream infection was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group, which also had 14 fewer days of hospitalization (95% CI, 9 to 20 fewer days) and a 32-percentage point increase in overall survival (95% CI, 16 to 47 percentage points) compared with the antibiotic group.

Limitations of the study include its observational nature and single-center design, as well as the fact that on average, patients treated with FMT presented with worse clinical conditions than those treated with antibiotics, the study authors noted. They added that differences in several baseline characteristics between the groups still remained after matching.

On the other hand, a separate brief report from the U.S. that was published on Oct. 30, 2019, by the New England Journal of Medicine and appeared in the Nov. 21, 2019, issue cautioned that FMT-associated bloodstream infections can be deadly. The report described two patients in whom extended-spectrum beta-lactamase-producing Escherichia coli bacteremia occurred after they had received FMT capsules in two independent clinical trials. One patient died.

Both cases were linked to the same stool donor through genomic sequencing, and a total of 22 patients received FMT capsules generated from this donor. The two ill patients had risk factors for bacteremia: cirrhosis with hepatic encephalopathy in one and hematologic dysplasia treated by means of hematopoietic-cell transplantation in the other. Both patients received oral antibiotics near the time of FMT.

Currently, at least 10,000 FMTs are performed each year in the U.S., an accompanying editorial noted. While it is reasonable to test FMT in rigorous clinical trials, the intervention may carry risks that can only be identified after the fact, the editorialist wrote. “Improved screening of FMT donors and of the material to be transplanted will certainly reduce the risks of infections by known agents,” the editorial said. “. . . Despite its seemingly innocuous, if unpleasant, aspect and possibility to do it oneself at home, FMT carries a risk of infectious hazards that needs to be taken seriously.”

Approval delays for high-cost OPAT common, associated with discharge to subacute care

Delays in the approval of outpatient parenteral antimicrobial therapy (OPAT) were common when high-cost drugs were prescribed, and they were associated with later discharge and higher costs, a recent study found.

The retrospective study included 200 adult patients discharged on high-priced OPAT antibiotics from one hospital in 2017. The antibiotics included daptomycin, ceftaroline, ertapenem, and the novel beta-lactam beta-lactamase inhibitor combinations. Fifty-nine of the patients (30%) experienced a prior authorization delay, defined as a response taking longer than one day. More patients with a prior authorization delay were discharged to a subacute care facility than to an outpatient setting (37 [63%] vs. 22 [37%]; P=0.001). Results of the study were published by Clinical Infectious Diseases on Oct. 31, 2019.

Image by Getty Images
Image by Getty Images

Patients whose OPAT was delayed by prior authorization had significantly more days of inpatient treatment (7 days vs. 3 days; P<0.001), longer duration of hospitalization (13 days vs. 7 days; P<0.001), and higher total direct hospital costs ($19,576 vs. $7,770; P<0.001). Delayed hospital discharge, which the study defined as hospitalization continuing after the day the patient was deemed medically stable for discharge, was significantly more common in patients with OPAT delays (53% vs. 15%; P<0.001). Delayed discharge was also more likely in patients going to a subacute care facility (adjusted odds ratio [OR], 2.623, 95% CI, 1.298 to 5.299) or having only public insurance (adjusted OR, 2.282, 95% CI, 1.194 to 4.360), while it was less common in those over age 64 years (adjusted OR, 0.430; 95% CI, 0.206 to 0.898).

The study authors concluded that prior authorization delays for high-priced OPAT are common. They noted that the association with care in a subacute care facility could potentially be explained by the payment structure for those facilities not routinely allowing for reimbursement for these medications. “There is a need for creative solutions in supply or payment to provide these medications without requiring patients to remain hospitalized to receive intravenous therapy,” the authors said.

They also called on physicians and hospitals to work to improve transitions of care and avoid barriers and delays for these patients. The fact that 93% of the study patients ultimately received their OPAT regimen is evidence that these barriers can eventually be overcome, the authors said. They recommended that clinicians undertake collaborative efforts to identify patients who should receive OPAT early during hospitalization and begin planning their transitions. “Early discussion with patients, caregivers and case management about the costs of care should be considered,” they said.

The study's findings may not be generalizable to facilities with different OPAT processes and patient populations, but the steps and delays in the prior authorization process are likely similar across the country, according to the authors. The study did not assess the appropriateness of antibiotic selection or cause and effect, among other limitations.

No association between contrast use and AKI seen in critically ill patients with normal kidney function

The risk of acute kidney injury (AKI) was not significantly increased in ICU patients with normal kidney function who received contrast compared to similar patients who did not receive it, a recent study found.

The retrospective observational study included ICU patients from a six-hospital health system in South Florida. Patients who had received low osmolar radiocontrast media were propensity matched (on baseline characteristics, admission diagnoses, comorbidities, and severity of illness) to unexposed controls to create 2,306 patient pairs. The primary outcome was AKI, defined as initial onset (stage 1) or increased severity, determined from serum creatinine. Results were published by CHEST on Oct. 25, 2019, and appeared in the April issue.

Patients who received contrast had an AKI risk of 19.3% compared to 18.0% in those who didn't, an insignificant difference (P=0.273). The study also found no association between contrast use and the pattern of AKI onset and recovery. Patients who developed AKI did have a significantly increased risk of hospital mortality (18.0% vs. 3.6%; P<0.001), but the risk ratio did not vary when stratified by contrast use. Multivariable regression analysis found factors other than the receipt of contrast were associated with AKI, including sepsis, metabolic disorders, diabetes, history of renal disease, and severity of illness.

Several other studies have also failed to find an association between contrast and AKI in critically ill patients, the study authors noted. Strengths of this study include its large, diverse sample of patients who were well matched between those with and without contrast exposure. Limitations include potential effects of unmeasured confounders and lack of data on fluid intake.

Based on the results, the authors concluded that contrast does not increase AKI risk in critically ill patients with normal kidney function enough that its use should be avoided when otherwise indicated. The study “adds to a growing body of evidence that the risk of AKI in relation to administration of contrast media has been overstated leading to unnecessary guidelines limiting its use and diverting the focus of preventive measures away from more significant susceptibilities,” the authors said.

Sex differences prevalent in acute MI presentation and treatment

Older women hospitalized for acute myocardial infarction (MI) have worse outcomes than men, and use of high-sensitivity troponin as a diagnostic indicator did not lead to improved treatment for women with suspected acute coronary syndrome (ACS) and myocardial injury, according to two recent studies of sex-related differences in cardiac care.

The first study analyzed data from SILVER-AMI, an observational study of 3,041 older patients hospitalized for acute MI. After stratification by MI subtype, that is, ST-segment elevation MI (STEMI) or non-ST-segment elevation MI (NSTEMI), patients were evaluated for differences in clinical presentation, functional impairments, management, and in-hospital complications by sex. The results were published by Circulation: Cardiovascular Quality and Outcomes on Oct. 14, 2019.

Image by Getty Images
Image by Getty Images

Of the 3,041 patients in the study, 1,695 (55.7%) were men and 1,346 (44.3%) were women. The NSTEMI group included 1,276 men and 968 women, while the STEMI group included 419 men and 378 women. Mean age for women versus men was 82.1 years versus 81.3 years in the NSTEMI group and 82.2 years versus 80.6 years in the STEMI group. Women were less likely than men to present with chest pain as their primary symptom (50.0% vs. 58.6% for NSTEMI [P<0.001] and 57.4% vs. 63.2% for STEMI [P=0.09]). Age-associated functional impairments at baseline were more common in women among patients with both types of acute MI.

Rates of obstructive coronary disease were lower in women with acute MI, mainly because they had lower rates of three-vessel or left main disease than men. Women with STEMI and NSTEMI were also less likely to undergo revascularization than men (87.3% vs. 93.3% [P=0.01] and 55.6% vs. 63.6% [P<0.001]) and were less likely to receive a statin (78.0% vs. 86.2% [P<0.01] and 70.7% vs. 75.2% [P=0.02]). Bleeding rates were significantly higher among women in the STEMI group (26.2% vs. 15.6%; P<0.001) but not in the NSTEMI group (17.8% vs. 15.7%; P=0.21), and women in both groups were more likely to have a bleeding event after percutaneous coronary intervention (22.6% vs. 14.8% [P=0.02] and 11.0% vs. 7.8% [P=0.04]).

The researchers noted that information about anticoagulant drugs given at admission or in the cardiac catheterization laboratory was not available and that their study was descriptive, among other limitations. They concluded that older women and men with acute MI differ significantly in presentation characteristics, management, coronary artery disease burden, and bleeding complications. “Recognition of higher rates of functional impairment among older women with [acute] MI and higher incidence of overall bleeding among older women with STEMI, driven by higher rates of nonmajor bleeding and bleeding following [percutaneous coronary intervention], represents a critical step toward optimizing in-hospital and postdischarge care for this vulnerable population,” they wrote.

The second study looked at whether using sex-specific diagnostic thresholds for high-sensitivity cardiac troponin I (hs-cTnI) in patients with suspected ACS would help reduce disparities in MI care between men and women. Consecutive patients from 10 hospitals in Scotland who had suspected acute ACS were enrolled in a stepped-wedge, cluster-randomized trial. A contemporary cardiac troponin I assay was used to guide clinical care for a validation phase of at least six months, and hospitals were then randomly assigned to early or late implementation of an hs-cTnI assay and sex-specific thresholds for myocardial injury, defined as a concentration above the 99th centile of 16 ng/L in women and 34 ng/L in men.

Cardiac troponin testing was done at presentation to the ED and was repeated six to 12 hours after symptom onset at the attending clinician's discretion. All hospitals measured cardiac troponin with both the contemporary assay and the hs-cTnI assay simultaneously throughout the trial. Only the results of the former were reported to the attending clinician during the validation phase, and only the results of the latter were reported during the implementation phase. Two physicians from the study's adjudication panel independently reviewed the records of patients with hs-cTnI levels above the 99th centile and determined whether they had had a MI according to the American Heart Association's Third Universal Definition of MI. The study's primary outcome was recurrent MI or cardiovascular death at one year. Three study authors received honoraria from Abbott Laboratories, which also provided cardiac troponin assay reagents, calibrators, and controls for the study free of charge. Results were published Oct. 14, 2019, by the Journal of the American College of Cardiology.

Overall, 48,282 patients were included in the trial, and of these, 22,562 (47%) were women and 25,720 (53%) were men. When sex-specific hs-cTnI thresholds were used, 42% more women and 6% more men were reclassified as having myocardial injury. However, women with myocardial injury diagnosed by sex-specific thresholds were still less likely than men to have percutaneous coronary intervention or coronary artery bypass grafting (15% vs. 34%; P<0.001) and to receive dual antiplatelet therapy (26% vs. 43%; P<0.001) or statins (16% vs. 26%; P=0.001), as well as other preventive therapies. Recurrent MI or cardiovascular death at one year occurred in 18% and 17% of women with myocardial injury before and after implementation of sex-specific thresholds (adjusted hazard ratio, 1.11; 95% CI, 0.92 to 1.33) versus 18% and 15% of men (adjusted hazard ratio, 0.85; 95% CI, 0.71 to 1.01).

The researchers noted that some MI diagnoses may have been misclassified and that their estimates of treatment efficacy could have been affected by confounding by indication, among other limitations. They concluded that using a hs-cTnI assay with sex-specific thresholds identified more women with myocardial injury with men but that despite the increase, women remained less likely to receive appropriate MI treatment. In addition, they said, implementation of the assay in clinical practice was not associated with substantial reductions in rates of subsequent MI or cardiovascular death in men or women.

An accompanying editorial pointed out several potential reasons why the reclassification rate with a high-sensitivity assay was higher in this study than in previous studies, including differences in study populations, differences in assays, and collection of samples at baseline and six to 12 hours after symptom onset rather than one to two hours. The editorialists also noted that sex and gender factors such as differences in presentation may independently affect diagnosis and outcomes. However, “It is clear from this study that simply improving diagnostic accuracy cannot remedy deeply embedded gender disparities in attitudes, practice, and outcome,” they wrote. “Simply put, if one does not act on the data, no diagnostic test will ever have additional worth.”

1 in 4 patients with malignant pleural effusion readmitted within a month

Among cancer patients with malignant pleural effusions (MPEs), readmissions were common and associated with a high risk of mortality, a recent study found.

The retrospective cohort study used 2014 data from the Nationwide Readmissions Database to identify 108,824 index hospitalizations for MPE and determine the rate and predictors of all-cause, unplanned, 30-day readmissions. Results were published by CHEST on Sept. 19, 2019, and appeared in the February issue.

A total of 27,900 unplanned readmissions occurred within 30 days of hospitalization for MPE, a rate of 25.6% (95% CI, 25.0% to 26.3%). The mortality rate during readmission to the hospital was 17.3% (95% CI, 16.6% to 18.1%). The mean cost per readmission was $15,452, which would result in total aggregate costs of more than $400 million per year in the U.S., the researchers calculated. Predictors of early readmission included Medicaid insurance, treatment with thoracentesis only, and discharge to a facility or home health care.

“There is a paucity of data regarding readmission rates in patients with MPE despite the high prevalence in the hospitalized population,” the study authors said. Treatment for MPE varies widely, they noted, and the study's finding of fewer readmissions in patients who had a definitive procedure for their MPE instead of receiving only thoracentesis should be considered by clinicians choosing a management strategy. The other factors that were found to predict readmissions could be used to target care transition interventions, such as early postdischarge follow-up, they said.

The mortality rate of patients who were readmitted should also be considered in practice, the authors recommended. “As MPE represents metastatic disease with poor prognosis, referral to palliative care should occur routinely in conjunction with, or at the time of, referral for pleural procedures,” they said. Future research should work to identify interventions that might prevent readmissions in these patients, the authors said.

Limitations of the study include its reliance on coding data, lack of data on whether readmissions were related to MPE, and the potential influence of death as a competing postdischarge risk on the results of the analysis.