Comparative Effectiveness of Fidaxomicin vs Vancomycin in Populations With Immunocompromising Conditions for the Treatment of Clostridioides difficile Infection: A Single-Center Study.

Background: Clostridioides difficile infection (CDI) is a leading cause of morbidity in immunocompromised hosts with increased risk of complications and recurrences. In this study, we examined the clinical effectiveness of fidaxomicin vs vancomycin in treating CDI in this patient population. Methods: This single-center retrospective study evaluated patients with CDI between 2011 and 2021. The primary outcome was a composite of clinical failure, relapse at 30 days, or CDI-related death. A multivariable cause-specific Cox proportional hazards model was used to test the relationship between treatment and the composite outcome, adjusting for confounders and treating death from other causes as a competing risk. Results: This study analyzed 238 patients who were immunocompromised and treated for CDI with oral fidaxomicin (n = 38) or vancomycin (n = 200). There were 42 composite outcomes: 4 (10.5%) in the fidaxomicin arm and 38 (19.0%) in the vancomycin arm. After adjustment for sex, number of antecedent antibiotics, CDI severity and type of immunosuppression, fidaxomicin use significantly decreased the risk of the composite outcome as compared with vancomycin (10.5% vs 19.0%; hazard ratio, 0.28; 95% CI, .08-.93). Furthermore, fidaxomicin was associated with 70% reduction in the combined risk of 30- and 90-day relapse following adjustment (hazard ratio, 0.27; 95% CI, .08-.91). Conclusions: The findings of this study suggest that the use of fidaxomicin for treatment of CDI reduces poor outcomes in patients who are immunocompromised.

A Clinical Model to Predict the Occurrence of Select High-risk Infections in the First Year Following Heart Transplantation.

Background: Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y. Methods: A retrospective cohort study of HT recipients (2000-2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application. Results: Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 103cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated. Conclusion: This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.

Sex- and age-based comparison of serum immunoglobulins following liver transplantation.

BACKGROUND: Over a quarter of organ transplant recipients have low immunoglobulin levels in their early post-transplant course, which is associated with increased risk of infection and mortality. Although immunoglobulin level varies by sex among healthy individuals, it is unknown how such differences are affected by transplant-related immunosuppression. This study compared post-liver transplant immunoglobulin G (IgG) between sexes at varying ages. METHODS: Serum specimens from a prospective cohort of 130 liver transplant recipients were analyzed. IgG was measured at time of transplant and from one-month post-transplant samples. Post-transplant IgG was compared between sexes using multivariable linear regression. Four age and sex categories were created (women<50, women≥50, men<50, men≥50) and the model repeated with this as the explanatory variable. The relationship between sex hormone concentrations and post-transplant IgG was also explored. Infection type and incidence were examined within groups. RESULTS: The cohort included 99 men, 31 women (mean age 53). In adjusted linear regression, post-transplant IgG was not significantly different by sex (p = 0.92). However, when broken into four categories by age and sex, the contrast in IgG levels between younger versus older patients was strikingly greater among women than among men. An interaction term including age and sex was statistically significant (p = 0.03). The combined age-sex categorical variable was also significantly associated with post-transplant IgG (p = 0.01). Finally, an association was identified between baseline estradiol level and post-transplant change in IgG (p = 0.04). CONCLUSIONS: Sex and age have an important relationship with post-transplant IgG with older women demonstrating lowest concentrations. Immunoglobulin levels have previously demonstrated association with post-transplant outcomes.

Impact of antimicrobial use in dogs on antimicrobial resistance and shared flora with human owners.

Transmission of bacteria between animals and humans in domestic households is increasingly recognized. We evaluated the presence of antimicrobial-resistant fecal bacteria in 8 dog-owner-dog pairs before and after the dog received amoxicillin-clavulanate. The study identified shared flora in the humans and dogs that were affected by antimicrobial administration.

Effecting the culture: Impact of changing urinalysis with reflex to culture criteria on culture rates and outcomes.

OBJECTIVE: To evaluate the impact of changes to urinalysis with reflex to culture (UARC) reflex criteria on culture performance and clinical decision outcomes. DESIGN: Retrospective study utilizing interrupted time series analysis from December 2018 to November 2020. Primary outcomes were measures of culture performance. Secondary outcomes were rates of antimicrobial prescription for suspected urinary tract infection (UTI) and catheter-associated urinary tract infection (CAUTI). We also assessed harmful events related to antimicrobial prescription for all causes and UTI, UTI symptoms, and sepsis. SETTING: A 415-bed, academic, tertiary-care, medical center. PATIENTS: Hospitalized adult patients with urine testing performed. INTERVENTION: UARC reflex criteria were changed on October 22, 2019, from ≥5×109/L white blood cells (WBCs) or trace leukocyte esterase or positive nitrite units on urinalysis to only ≥15×109/L WBCs. RESULTS: The study included 11,322 unique UARC tests. We detected a significant decrease in the rate of urine cultures performed from UARC after the intervention (32.5-8.7 cultures per 1,000 patient days; P < .001), with improved diagnostic efficacy (ie, culture positivity increased from 34.8% to 62.1%). CAUTI rates did not change. We detected a significant decrease in antimicrobial prescription rates (P = .05), this was primarily driven by preintervention changes. One case of sepsis occurred secondary to a missed UTI, and UTIs were rarely missed after the intervention. CONCLUSIONS: Implementation of a stricter UARC reflex criterion was associated with a decrease in culture rates with improved diagnostic efficacy without significant adverse events. Continued education is needed to change antimicrobial prescribing practices.

Impact of provider-selected indication requirement on urine test utilization and positivity.

Objective: To evaluate the impact of the addition of an indication specification requirement to isolated urine-culture ordering on testing utilization. Design: Retrospective study utilizing interrupted time series analysis with negative binomial regression. The preintervention period was October 1, 2018-November 11, 2019, and the postintervention period was November 12, 2019-October 31, 2020. The primary outcome was isolated culture rate per 1,000 patient days. Secondary outcomes were the proportion of all urine tests ordered as isolated urine culture and culture positivity. An exploratory analysis assessed the appropriateness of selected testing indications. Setting: A 415-bed, urban, academic medical center. Patients: Adult patients with urine testing performed during hospital admission. In total, 1,494 unique isolated urine-culture orders were included in the analysis. Interventions: On November 12, 2019, the laboratory order interface was changed to require the ordering provider to select an indication for isolated urine culture. Results: Isolated urine-culture rates did not significantly change after the intervention (11.2-7.8 cultures per 1,000 patient days; P = .17) nor did culture positivity (26.9% vs 26.8%). Most ordering providers left the indication for testing blank, and of those charts reviewed, 67% did not have a documented condition for which isolated urine culture was the most appropriate initial test. Conclusions: The addition of an order-specification requirement for isolated urine-culture testing did not significantly affect ordering practices. The test remains overused as the initial diagnostic evaluation for a suspected urinary tract infection. Further provider education and continued changes in provider workflow are needed to achieve lasting change in practice.

Female sex and advanced age are associated with invasive cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Limited data exist to describe sex-based differences in the severity of cytomegalovirus (CMV) infection after solid organ transplant (SOT). We sought to identify if a difference exists in likelihood of tissue-invasive disease between male and female SOT recipients and to understand how age affects this relationship. METHODS: A retrospective cohort of 180 heart, liver, and kidney recipients treated for CMV was examined. A logistic regression model was developed to assess the relationship between female sex and CMV type (noninvasive vs. invasive). A secondary regression analysis looked at the relationship of invasive CMV with a variable combining sex with age above or below 50. RESULTS: There were 37 cases of proven or probable invasive CMV, occurring in 30% of females versus 16% of males. After adjustment for potential confounders, females with CMV infection were significantly more likely to have invasive disease (odds ratio (OR) 2.69, 95% confidence interval (CI) 1.25-5.90, p = .01). Females 50 years or older were at particular risk compared with males under 50 years (adjusted OR 4.54, 95% CI 1.33-18.83, p = .02). CONCLUSION: Female SOT recipients with CMV in our cohort were more likely than males to have tissue-invasive disease, with the highest risk among older females. Further prospective studies are warranted to explore underlying immunologic mechanisms.

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. METHODS: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. RESULTS: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). CONCLUSIONS: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.

In Vitro Evaluation of the Activity of Aztreonam-Avibactam against 341 Recent Clinical Isolates of Anaerobes.

Aztreonam-avibactam is under clinical development for multidrug-resistant Gram-negative infections. We evaluated in vitro activity against 341 recent clinical isolates. The addition of avibactam to aztreonam had no effect on the anaerobic activity of aztreonam. IMPORTANCE This work shows that aztreonam-avibactam lacks activity against anaerobic organisms.

Difference in absolute lymphocyte count among male and female heart transplant recipients.

The impact of sex on immune composition in the setting of solid organ transplantation is unknown. Immunocompetent men and women have quantitative differences in multiple markers of immunity, including lymphocyte subsets. Lymphocytes are of particular interest given the routine use of medications targeted at cell-mediated immunity. The objective of this retrospective cohort study was to compare absolute lymphocyte count (ALC) measurements of male and female heart recipients immediately before, and 1 month after, transplantation. Data was collected on 375 adult recipients (104 female and 271 male) from 2000 to 2018 at a single center. Mean ALC was compared using Student's t-test. Women had higher mean ALC both at baseline (female 1.6 × 103 cells/µl vs. male 1.3 × 103 cells/µl; P < .001) and at 1 month post-transplantation (mean 1.2 × 103 cells/µl vs. .8 × 103 cells/µl; P < .001). This finding could have important implications for sex-based differences in predisposition to rejection or response to infection or vaccination.

Factors associated with neutropenia post heart transplantation.

BACKGROUND: Neutropenia is a serious complication following heart transplantation (OHT); however, risk factors for its development and its association with outcomes is not well described. We sought to study the prevalence of neutropenia, risk factors associated with its development, and its impact on infection, rejection, and survival. METHODS: A retrospective single-center analysis of adult OHT recipients from July 2004 to December 2017 was performed. Demographic, laboratory, medication, infection, rejection, and survival data were collected for 1 year post-OHT. Baseline laboratory measurements were collected within the 24 hours before OHT. Neutropenia was defined as absolute neutrophil count ≤1000 cells/mm3. Cox proportional hazards models explored associations with time to first neutropenia. Associations between neutropenia, analyzed as a time-dependent covariate, with secondary outcomes of time to infection, rejection, or death were also examined. RESULTS: Of 278 OHT recipients, 84 (30%) developed neutropenia at a median of 142 days (range 81-228) after transplant. Factors independently associated with increased risk of neutropenia included lower baseline WBC (HR 1.12; 95% CI 1.11-1.24), pre-OHT ventricular assist device (1.63; 1.00-2.66), high-risk CMV serostatus [donor positive, recipient negative] (1.86; 1.19-2.88), and having a previous CMV infection (4.07; 3.92-13.7). CONCLUSIONS: Neutropenia is a fairly common occurrence after adult OHT. CMV infection was associated with subsequent neutropenia, however, no statistically significant differences in outcomes were found between neutropenic and non-neutropenic patients in this small study. It remains to be determined in future studies if medication changes in response to neutropenia would impact patient outcomes.

Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: A systematic literature review of real-world evidence.

Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug-induced immunosuppression. A comprehensive review of published literature reporting real-world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real-world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R- and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one-fourth of KTR developed CMV infection. Age and D+/R- CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management.

Antiviral treatment approaches for cytomegalovirus prevention in kidney transplant recipients: A systematic review of randomized controlled trials.

Various CMV anti-viral (AV) preventive strategies have been utilized in KTRs. We examined efficacy, safety and costs of CMV-AV prevention strategies in KTRs using a systematic literature review (SLR) of randomized controlled trials (RCTs) publications indexed in MEDLINE and Embase (from inception to November 2018). Thirty RCTs met inclusion criteria with 22 unique AV preventive strategies. Prophylaxis was associated with significantly lower rates of CMV infection/disease (CMVi/d) compared to no prophylaxis (pooled odds ratio, pOR with 95% confidence interval (CI): CMVi: 0.33; 0.19, 0.57; CMVd: 0.27; 0.19; 0.39). Preemptive therapy (PET) had lower rates of CMVd (0.29; 0.11, 0.77), and medical costs compared to no PET. Prophylaxis had significantly lower rates of early CMVi/d, and higher rates of late CMVi and hematological adverse events (leukopenia, 2.93; 1.22, 7.04), and similar overall medical costs compared to PET. Studies involving head-to-head comparison of different prophylaxis approaches showed mixed findings with respect to optimum dose, duration and route of administration on CMV outcomes. Although there was heterogeneity across populations and interventions, both prophylaxis and PET strategies reduced CMVi/d compared to no prophylaxis/PET and had differential safety profile in terms of hematological adverse events. For comprehensiveness we did not limit study inclusion based on date; the wide time-period may have contributed to the heterogeneity in prevention approaches which subsequently made pooling studies a challenge. Despite demonstrated efficacy of prophylaxis/PET, our findings highlight the potential need of a novel intervention with a better safety profile and perhaps improved outcomes.

Association Between Lymphopenia at 1 Month Posttransplant and Infectious Outcomes or Death in Heart Transplant Recipients.

BACKGROUND: Cell-mediated immunity is a specific target of several medications used to prevent or treat rejection in orthotopic heart transplantation. Low absolute lymphocyte count (ALC) has potential to be a useful and accessible clinical indicator of overall infection risk. Though some studies have demonstrated this association in other transplant populations, it has not been assessed in heart transplant recipients. METHODS: A single-center retrospective cohort study examined adult heart transplant recipients transplanted between 2000 and 2018. The exposure of interest was ALC ≤0.75 × 103 cells/µL at 1 month posttransplant, and the primary endpoint was a composite outcome of infection (including cytomegalovirus [CMV], herpes simplex I/II or varicella zoster virus [HSV/VZV], bloodstream infection [BSI], invasive fungal infection [IFI]) or death occurring after 1 month and before 1 year posttransplant. A multivariable Cox proportional hazards model was created to control for confounders identified using clinical judgment and statistical criteria. RESULTS: Of 375 subjects analyzed, 101 (27%) developed the composite outcome (61 CMV, 3 HSV/VZV, 19 BSI, 10 IFI, 8 deaths). Lymphopenia (ALC ≤0.75 × 103 cells/µL) at 1 month was associated with a >2-fold higher rate of the composite outcome (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.47-3.46]; P < .001) compared to patients without lymphopenia at 1 month. After adjustment for confounding variables, the presence of lymphopenia remained statistically significantly associated with the composite outcome (HR, 1.72 [95% CI, 1.08-2.75]; P = .02). CONCLUSIONS: ALC measured at 1 month after heart transplant is associated with an increased risk of infectious outcomes or death in the ensuing 11 months. This is a simple, accessible laboratory measure.

Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids.

Antibiotic treatment is a standard therapy for Clostridioides difficile infection, but dysbiosis of the gut microbiota due to antibiotic exposure is also a major risk factor for the disease. Following an initial episode of C. difficile infection, a relentless cycle of recurrence can occur, where persistent treatment-related dysbiosis predisposes the patient to subsequent relapse. This study uses a longitudinal study design to compare the effects of a narrow-spectrum (ridinilazole) or broad-spectrum antibiotic (vancomycin) on intestinal bile acid profiles and their associations with gut bacteria over the course of C. difficile infection treatment. At the end of treatment (day 10), subjects receiving vancomycin showed a nearly 100-fold increase in the ratio of conjugated to secondary bile acids in their stool compared with baseline, whereas subjects receiving ridinilazole maintained this ratio near baseline levels. Correlation analysis detected significant positive associations between secondary bile acids and several Bacteroidales and Clostridiales families. These families were depleted in the vancomycin group but preserved at near-baseline abundance in the ridinilazole group. Enterobacteriaceae, which expanded to a greater extent in the vancomycin group, correlated negatively and positively with secondary and conjugated primary bile acids, respectively. Bile acid ratios at the end of treatment were significantly different between those who recurred and those who did not. These results indicate that a narrow-spectrum antibiotic maintains an intestinal bile acid profile associated with a lowered risk of recurrence.NEW & NOTEWORTHY This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent's favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment.

The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and long-term survival in SOT recipients. METHODS: We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10 years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying. RESULTS: About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8 years (IQR 0.8-6.6 years). Median follow-up among the 108 survivors was 7.4 years (IQR 3.7-10 years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6 months of treatment completion. Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P = .10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P = .09). CONCLUSIONS: Mortality following CMV remains high even in the valganciclovir era. Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed.

Prospective Observational Study Comparing Sepsis-2 and Sepsis-3 Definitions in Predicting Mortality in Critically Ill Patients.

BACKGROUND: Sepsis definitions have evolved, but there is a lack of consensus over adoption of the most recent definition, Sepsis-3. We sought to compare Sepsis-2 and Sepsis-3 in the classification of patients with sepsis and mortality risk at 30 days. METHODS: We used the following definitions: Sepsis-2 (≥2 systemic inflammatory response syndrome criteria + infection), Sepsis-3 (prescreening by quick Sequential Organ Failure Assessment [qSOFA] of ≥2 of 3 criteria followed by the complete score change ≥2 + infection), and an amended Sepsis-3 definition, iqSOFA (qSOFA ≥2 + infection). We used χ 2 or Wilcoxon rank-sum tests, receiver-operator characteristic curves, and survival analysis. RESULTS: We enrolled 176 patients (95% in an intensive care unit, 38.6% female, median age 61.4 years). Of 105 patients classified by Sepsis-2 as having sepsis, 80 had sepsis per Sepsis-3 or iqSOFA (kappa = 0.72; 95% confidence interval [CI], 0.62-0.82). Twenty-five (14.8%) died (20 of 100 with sepsis per Sepsis-2 [20%], and 20 of 77 [26.0%] with sepsis per Sepsis-3 or iqSOFA). Results for Sepsis-3 and iqSOFA were identical. The area under the curve of receiver-operator characteristic (ROC) curves for identifying those who died were 0.54 (95% CI, 0.41-0.68) for Sepsis-2, 0.84 (95% CI, 0.74-0.93) for Sepsis-3, and 0.69 (95% CI, 0.60-0.79) for iqSOFA (P < .01). Hazard ratios for death associated with sepsis were greatest for sepsis or septic shock per Sepsis-3. CONCLUSIONS: Sepsis-3 and iqSOFA were better at predicting death than Sepsis-2. Using the SOFA score might add little advantage compared with the simpler iqSOFA score.

The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study.

BACKGROUND: Despite well-defined criteria for use of antibiotics in patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), their overuse is widespread. We hypothesized that following implementation of a molecular multiplex respiratory viral panel (RVP), AECOPD patients with viral infections would be more easily identified, limiting antibiotic use in this population. The primary objective of our study was to investigate if availability of the RVP decreased antibiotic prescription at discharge among patients with AECOPD. METHODS: This is a single center, retrospective, before (pre-RVP) - after (post-RVP) study of patients admitted to a tertiary medical center from January 2013 to March 2016. The primary outcome was antibiotic prescription at discharge. Groups were compared using univariable and multivariable logistic-regression. RESULTS: A total of 232 patient-episodes were identified, 133 following RVP introduction. Mean age was 68.1 (pre-RVP) and 68.3 (post-RVP) years respectively (p = 0.88). Patients in pre-RVP group were similar to the post-RVP group with respect to gender (p = 0.54), proportion of patients with BMI < 21(p = 0.23), positive smoking status (p = 0.19) and diagnoses of obstructive sleep apnea (OSA, p = 0.16). We found a significant reduction in antibiotic prescription rate at discharge in patients admitted with AECOPD after introduction of the respiratory viral assay (pre-RVP 77.8% vs. post-RVP 63.2%, p = 0.01). In adjusted analyses, patients in the pre-RVP group [OR 2.11 (CI: 1.13-3.96), p = 0.019] with positive gram stain in sputum [OR 4.02 (CI: 1.61-10.06), p = 0.003] had the highest odds of antibiotic prescription at discharge. CONCLUSIONS: In patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), utilization of a comprehensive respiratory viral panel can significantly decrease the rate of antibiotic prescription at discharge.

Reactivation of latent cytomegalovirus infection in patients with rheumatologic disease: a case-control study.

The disease burden, risk factors and clinical sequelae of CMV reactivation in patients with rheumatologic conditions is poorly understood. We have described a cohort with underlying rheumatic disease and CMV, and compared a subgroup with systemic lupus erythematosus (SLE) to controls to identify potential risk factors for CMV reactivation. Adults with rheumatic disease and CMV infection from 2000-2015 were identified. SLE cases were matched 3:1 with controls based on age, sex and year of admission, and compared. Fourteen patients were included (6 SLE, 4 rheumatoid arthritis, 2 sarcoidosis, 1 psoriatic arthritis, 1 microscopic polyangiitis). Seven had viremia alone, the remainder tissue-invasive disease. Thirteen received glucocorticoids prior to CMV reactivation. Fever was the most common symptom, and coinfections were seen in eight including four with bacteremia. Thirteen received antiviral therapy (median 33 days), four died during hospitalization. Six patients with underlying SLE and CMV reactivation were compared to 18 SLE controls. Cases received more glucocorticoids prior to admission (median 36.5 vs. 2.5 mg/day, p = 0.006), had longer hospitalizations (median 47 vs. 7 days, p = 0.006) and more coinfections (67% vs. 17%, p = 0.04). There were no significant differences in symptoms at presentation. CMV reactivation occurs in patients with rheumatologic disease, can result in severe clinical sequelae, and is difficult to distinguish from a flare of the underlying disease. Patients with CMV received higher doses of glucocorticoids and developed more co-infections. CMV should be considered during the evaluation of a febrile illness in this complex patient population.

Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of diarrhea in the pre- and post-transplant period. Diarrhea in an organ transplant recipient may result in significant morbidity including dehydration, increased toxicity of medications, and rejection. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common. Further, noninfectious causes including medication toxicity, inflammatory bowel disease, post-transplant lymphoproliferative disease, and malignancy can also result in diarrhea in the transplant population. Management of diarrhea in this population is directed at the cause of the diarrhea, instituting therapy where appropriate and maintaining proper hydration. Identification of the cause to the diarrhea needs to be timely and focused.