Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Epidemiology and Outcomes of Community-Acquired Escherichia coli Pneumonia.

BACKGROUND: E. coli is an under-recognized cause of bacterial community-acquired pneumonia (CAP). The objective of this study was to describe the epidemiology, risk factors, and outcomes of community-acquired Escherichia coli pneumonia in comparison with other gram-negative and pneumococcal pneumonias. METHODS: We conducted a large retrospective cohort study of adult patients admitted with pneumonia to 173 US hospitals included in the Premier Research database from July 2010 to June 2015. Patients were included if they had a principal diagnosis code for pneumonia or a principal diagnosis of respiratory failure or sepsis with a secondary diagnosis of pneumonia and had a positive blood or respiratory culture obtained on hospital day 1. The primary outcome was in-hospital case fatality. Secondary outcomes included intensive care unit admission, invasive mechanical ventilation, and use of vasopressors. RESULTS: Of 8680 patients with pneumonia and positive blood or respiratory cultures, 1029 (7.7%) had E. coli CAP. Patients with E. coli pneumonia were older and more likely to have a principal diagnosis of sepsis. Patients with E. coli pneumonia had significantly higher case fatality than patients with pneumococcal pneumonia (adjusted odds ratio, 1.55; 95% CI, 1.23-1.97), but it was not significantly different than other gram-negative pneumonias (adjusted odds ratio, 1.06; 95% CI, 0.85-1.32). Approximately 36% of the isolates were resistant to fluoroquinolones; 9.3% were resistant to ceftriaxone. CONCLUSIONS: E. coli is an important cause of severe CAP; with mortality that was higher than pneumococcal pneumonia but similar to other gram-negative pneumonias. The rate of fluoroquinolone resistance was high, and empiric fluoroquinolones should be used with caution in these patients.

Matched retrospective study of infective endocarditis among solid organ transplant recipients compared to non-transplant: Seven-year experience in a US Referral Center.

BACKGROUND: Infective endocarditis (IE) is a rare complication following solid organ transplant (SOT); data on the clinical features and outcomes of IE in SOT recipients in the modern era are limited. METHODS: We conducted a single-center retrospective cohort study of IE diagnosed from 1/2008-12/2014 in SOT recipients, who were matched by age and microorganism to cases of IE in non-SOT, to describe the clinical features and outcomes. RESULTS: There were 14 cases of IE identified in SOT recipients matched to 56 non-SOT controls. Median time from transplant to IE was 1017 days (IQR 379-1830). Compared to non-SOT patients, SOT patients were more likely to be undergoing current hemodialysis (16% vs 36%) and to possess indwelling central venous catheters within the 30 days prior to diagnosis of IE (27% vs 50%). No SOT patients had documented drug use as a risk factor for IE whereas 6 (11%) non-SOT did. Enterococcus was the most common etiologic agent and was isolated in 50% of cases; only one fungal infection was identified, a mixed infection with Candida. Thirty-day mortality was 14% in SOT patients, significantly higher versus no deaths in non-SOT (P = .037). CONCLUSIONS: The present study illustrates a change in epidemiology of IE in SOT patients characterized by IE that generally occurs more than one-year post-transplant, is due to bacterial infection rather than fungus, and appears to be health care associated. Multicenter studies are merited to explore transplant-specific risk factors for IE in the special population of SOT patients.

Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients.

The addition of toxin enzyme immunoassay (EIA) to nucleic acid amplification tests, including PCR, creates challenges in the diagnosis and management of Clostridioides difficile infection (CDI). There are limited data in large cohorts, with discordant results, that is, PCR-positive/EIA-negative (PCR+/EIA-) results. We conducted a retrospective cohort study on all PCR+/EIA- adult inpatients and assessed CDI-related complications and clinical failure. We identified 240 individuals. Twenty-three (9.6%) patients experienced a CDI-related complication, including 2 cases of megacolon, 1 colectomy, and 22 intensive care unit (ICU) admissions. In multivariable logistic regression analyses, baseline severe disease by Infectious Diseases Society of America (IDSA) criteria (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.88 to 18.1; P = 0.002), baseline fulminant colitis (OR, 84.7; 95% CI, 14.3 to 500; P < 0.001), fever of >38.5°C (OR, 4.61; 95% CI, 1.42 to 15.0; P = 0.011), and proton pump inhibitor (PPI) use (OR, 3.50; 95% CI, 1.19 to 10.3; P = 0.023) were associated with increased odds of CDI-related complications. For 67 PCR+/EIA- patients who did not receive complete treatment, clinical failure was observed in 10 (15%) patients. A comparison of PCR+/EIA- patients who received complete treatment to all 112 PCR+/EIA+ patients showed no differences in CDI-related complications (11% and 13% for PCR+/EIA- and PCR+/EIA+ patients, respectively), 60-day all-cause mortality (17% and 18% for PCR+/EIA- and PCR+/EIA+ patients, respectively), or recurrent CDI (7% and 9% for PCR+/EIA- and PCR+/EIA+ patients, respectively). Predictors of CDI-attributable complications among PCR+/EIA- patients include baseline severe disease by IDSA criteria, baseline fulminant colitis, and fever of >38.5°C. Identifying the subgroup of PCR+/EIA- patients who could have true disease, and therefore allowing them to be targeted for treatment, is critical.

Itraconazole vs. posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia undergoing intensive chemotherapy: A retrospective study.

OBJECTIVE: The objective of this study was to compare itraconazole with posaconazole for antifungal prophylaxis in acute myeloid leukemia (AML) patients undergoing intensive chemotherapy. METHODS: Adult patients with AML received either itraconazole or posaconazole for antifungal prophylaxis while undergoing intensive chemotherapy. The primary endpoint was incidence of prophylaxis failure (change in antifungal agent due to suspected invasive fungal infection [IFI], drug intolerance, drug interaction, or adverse event). RESULTS: From February 2016 to January 2018, 90 patients were included in the itraconazole group and 45 patients in the posaconazole group. Prophylaxis failure occurred in 88% of itraconazole recipients compared with 33% of posaconazole recipients (P<0.001). The primary reason for prophylaxis failure with itraconazole was suspected IFI (58%) whereas for posaconazole, failure predominantly related to drug interaction (60%). An antifungal regimen was continued upon discharge in 47% of itraconazole recipients compared with 9% of posaconazole recipients (P<0.001). The use of breakthrough IFI diagnostic tests was not significantly different in the two groups. A larger proportion of drug concentrations were collected in the posaconazole group. CONCLUSIONS: In AML patients undergoing intensive chemotherapy, posaconazole was associated with significantly lower rates of prophylaxis failure and less need for continued antifungal therapy on discharge compared with itraconazole.

Retrospective study evaluating the performance of risk factors for invasive mold infections in liver transplantation.

BACKGROUND: Mold infections in liver transplant are associated with high mortality. Guidelines recommend prophylaxis targeted against mold based upon risk factors of fulminant hepatic failure, retransplantation, reoperation, and renal replacement therapy post-transplant. It is not known if these factors identify risk of mold infection at every center. METHODS: A retrospective study was conducted of adult liver transplant recipients at a single center from 2010 to 2014. The association between risk factors and invasive mold infection and effect of antifungal prophylaxis were determined. RESULTS: Five hundred thirty-four liver transplant recipients were identified. The overall incidence of invasive mold infection was 0.9% (N = 5). The incidence in patients with (N = 128) and without (N = 406) risk factors was 0.78% and 0.98%, respectively. Antifungal prophylaxis with mold activity was administered to 23/128 (18%) with risk factors, and none developed infection. No mold-active prophylaxis was given to 105/128 (82%) with risk factors, and incidence of mold infection was 0.95% (N = 1). Number needed to treat was 105. CONCLUSIONS: Traditional risk factors for mold infection in liver transplant performed poorly. These results underscore the importance of transplant center-specific data to inform adoption of an antifungal prophylactic strategy. Studies are needed to determine alternative risk factors to facilitate appropriate targeting of antifungals.

Real-world use-Isavuconazole at a large academic medical center.

BACKGROUND: Isavuconazole use in the real-world setting has not been extensively described. Subgroups of patients with particular prognostic significance, such as previous triazole prophylaxis or treatment and the important subgroup treated empirically for invasive fungal infection, have beforehand been excluded from trials. OBJECTIVES: We aimed to determine treatment response and safety in these patients at a large US transplant and cancer centre. PATIENTS/METHODS: We conducted a retrospective cohort study of all adult inpatients administered ≥3 doses of isavuconazole between June 2015 and October 2017. RESULTS: Ninety-one adults were identified. Six (7%) received primary prophylaxis, 10 (11%) treatment then secondary prophylaxis and 75 (82%) treatment only. Overall treatment response was 62%. Six-week mortality was 24%. Sixty-three per cent of 32 patients treated with isavuconaozle following prophylaxis with another antifungal agent exhibited a treatment response. Among 49 patients switched from treatment with another agent, 53% had a treatment response. Thirty-four patients received isavuconazole empirically, and 65% demonstrated a treatment response. Individuals given isavuconazole prophylaxis developed no breakthrough invasive fungal infections. One patient discontinued isavuconazole due to hepatotoxicity. CONCLUSIONS: Real-world isavuconazole use appears safe and is associated with treatment responses in varied patients including critically important subgroups previously unreported.

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

A pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus viremia in ambulatory solid organ transplant recipients.

BACKGROUND: There is a growing need for robust antimicrobial stewardship interventions in both ambulatory and solid organ transplant (SOT) populations. METHODS: A retrospective quasi-experiment was conducted to evaluate the impact of a pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus (CMV) viremia in ambulatory SOT recipients. The intervention consisted of (a) real-time CMV DNA surveillance and result notification conducted by the pharmacist and (b) recommendations for the optimization of drug therapy provided at the time of result notification. The intervention period was compared to a pre-intervention period of usual care. Of 431 adult SOT recipients who had an initial quantifiable CMV viral load in the ambulatory setting, 185 received antiviral induction therapy and were included for analysis. RESULTS: Significantly fewer patients in the intervention period reached a CMV viral load >10 000 IU/mL immediately prior to treatment (10.6% vs 27.3%; P = 0.004), and a significantly greater proportion of patients in the intervention period achieved CMV eradication at 21 days (84.5% vs 71.7%; P = 0.038). Additional differences favoring the intervention period were antiviral initiation within 5 days of the first quantifiable CMV DNA (62.4% vs 55.0%; P = 0.02) and time-to-CMV eradication (25.5 vs 28.9 days; P = 0.003). Although not significant, there were also numerical reductions in CMV-related hospital admissions (11.9% vs 19.0%; P = 0.188) and CMV disease (5.9% vs 12.0%; P = 0.151) during the intervention period, as well as fewer episodes of CMV resistance at 1-year (2.3% vs 4.0%; P = 0.689). CONCLUSION: Together, these findings suggest a potential role for pharmacist involvement in CMV surveillance and treatment optimization in ambulatory SOT recipients.

Screening recipients of increased risk donor organs: A multicenter retrospective study.

Organ Procurement & Transplantation Network policy requires post-transplant screening of recipients of organs from donors at increased risk for transmission of HIV, hepatitis B virus, and hepatitis C virus. Available data suggest that follow-up testing of recipients is not routinely conducted. Data on increased risk donors and recipients of their organs from 2008 to 2012 were retrospectively collected from 6 transplant centers after IRB approval. Descriptive statistics were performed. About 363 (60%) recipients were screened for transmission of HIV, HBV, and/or HCV at some time point; 257 (70.8%) within 90 days of transplant. The type of test used to screen for infection was variable with many recipients (25%-43%) screened with serology alone. Our results reveal that post-transplant screening for HIV, HBV, and HCV in recipients of increased risk donor organs did not universally occur and testing methods were variable.

Carbapenem-resistant Klebsiella pneumoniae urinary tract infection following solid organ transplantation.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging pathogen with a devastating impact on organ transplant recipients (OTRs). Data describing urinary tract infections (UTIs) due to CRKP, compared to extended-spectrum ß-lactamase (ESBL)-producing and susceptible K. pneumoniae, are lacking. We conducted a retrospective cohort study comparing OTRs with a first episode of UTI due to CRKP, ESBL-producing K. pneumoniae, or susceptible K. pneumoniae. We identified 108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producing K. pneumoniae, and 64 (60%) due to susceptible K. pneumoniae. Compared to susceptible K. pneumoniae (27%), patients with UTIs due to CRKP or ESBL-producing K. pneumoniae were more likely to have a ≥ 24-hour stay in the intensive care unit (ICU) before or after development of the UTI (64% and 77%, respectively; P < 0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay prior to UTI with CRKP or ESBL-producing K. pneumoniae (7 and 8 days, respectively) were significantly longer than that for susceptible K. pneumoniae (1 day; P < 0.001). Clinical failure was observed for 8 patients (36%) with CRKP, 4 (18%) with ESBL-producing K. pneumoniae, and 9 (14%) with susceptible K. pneumoniae (P = 0.073). Microbiological failure was seen for 10 patients (45%) with CRKP, compared with 2 (9%) with ESBL-producing K. pneumoniae and 2 (3%) with susceptible K. pneumoniae (P < 0.001). In multivariable logistic regression analyses, CRKP was associated with greater odds of microbiological failure (versus ESBL-producing K. pneumoniae: odds ratio [OR], 9.36, 95% confidence interval [CI], 1.94 to 72.1; versus susceptible K. pneumoniae: OR, 31.4, 95% CI, 5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length of stay, and microbiological failure among OTRs with UTIs. Greater numbers are needed to determine risk factors for infection and differences in meaningful endpoints associated with carbapenem resistance.

Ebola virus: questions, answers, and more questions.

Ebola virus causes a hemorrhagic fever with a high case-fatality rate. Treatment remains supportive although a variety of specific treatments are still in the early stages of investigation. This report reviews the clinical virology of Ebola virus, the reported proposed treatments, and the current outbreak.

Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections.

Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status.

INTRODUCTION: Cryptococcosis is an invasive fungal infection causing substantial morbidity and mortality. Prognostic factors are largely derived from trials conducted prior to the modern era of antifungal and potent combination antiretroviral therapies, immunosuppression, and transplantation. Data describing the clinical features and predictors of mortality in a modern cohort are needed. METHODS: We conducted a retrospective cohort study of patients at our institution diagnosed with cryptococcosis from 1996 through 2010. Data included demographics, clinical features, diagnostics, treatment, and outcomes. RESULTS: We identified 302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%) organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT) patients including 39 with no identifiable immunodeficiency. Mean age was 49 years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90 days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR 5.09, 95% CI 2.54-10.22) and baseline opening pressure >25 cmH2O (OR 2.93, 95% CI 1.25-6.88) were associated with increased odds of mortality; HIV-positive patients (OR 0.46, 95% CI 0.19-1.16) and OTRs (OR 0.46, 95% CI 0.21-1.05) had lower odds of death compared to NHNT patients. CONCLUSIONS: Predictors of mortality from cryptococcosis in the modern period include cryptococcemia, high intracranial pressure, and NHNT status while drug(s) used for induction and historical prognostic factors including organ failure syndromes and hematologic malignancy were not associated with mortality.

Antifungal therapy and length of hospitalization in transplant patients with invasive aspergillosis.

The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed.

Pulmonary cryptococcosis.

Cryptococcosis is an invasive fungal infection (IFI), caused predominantly by Cryptococcus neoformans or Cryptococcus gattii, that affects both immunocompromised (IC) and non-IC patients. Although the most serious disease manifestation is meningoencephalitis, cryptococcal pneumonia is underdiagnosed and may disseminate to the central nervous system (CNS) and other sites depending upon host defenses and administration of appropriate antifungal therapy. The clinical presentation of pulmonary cryptococcosis varies along a spectrum from asymptomatic infection to severe pneumonia and respiratory failure, and the radiological presentation can be characterized by an array of findings, including nodules, consolidation, cavitary lesions, and a diffuse interstitial pattern. Diagnosis most often relies upon isolation of Cryptococcus from a pulmonary specimen in the appropriate clinical and radiological context. Treatment recommendations include induction therapy with an amphotericin B preparation and flucytosine for IC patients and those with severe disease and fluconazole for mild-to-moderate, localized disease. Knowledge of the pathophysiology, epidemiology, clinical presentation, and treatment of pulmonary cryptococcosis may lead to greater recognition of this underdiagnosed IFI and improved outcomes.