IntroductionCryptococcosis 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.MethodsWe 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.ResultsWe 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.ConclusionsPredictors 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.

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.

c 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 ␤-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.

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.

Summary 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.

Together, these findings suggest a potential role for pharmacist involvement in CMV surveillance and treatment optimization in ambulatory SOT recipients.

Objective To describe the epidemiology, risk factors and outcomes of community-acquired Escherichia coli pneumonia in comparison to other gram-negative and pneumococcal pneumonias. Methods E.coli is an under recognized cause of bacterial community-acquired pneumonia (CAP). We conducted a large retrospective cohort study of adult patients admitted with pneumonia to 173 US hospitals included in Premier Research database from July 2010–June 2015. Patients were included if they had principal diagnosis code for pneumonia, or a principal diagnosis of respiratory failure or sepsis with 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 (ICU) admission, invasive mechanical ventilation (IMV) and use of vasopressors. Results Of 8,680 patients with pneumonia and positive blood or respiratory cultures, 1,029 (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 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 higher mortality 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.

Although infection accounts for a substantial burden of morbidity and mortality among solid organ transplant (SOT) recipients, infective endocarditis (IE) remains a relatively uncommon complication. It has been shown that the observed incidence of IE in SOT patients ranges from 1% to 1.7%, 1,2 which is markedly higher than the 5-7.9 cases per 100 000 reported in non-SOT. 3 Recent studies in non-SOT patients show a changing epidemiology characterized by an increase in incidence of IE 4 with concomitant increase in health care-associated IE. 5,6 Data regarding SOT patients specifically, who may be at greater risk for IE due to extensive healthcare exposure, organ failure syndromes, and need for immunosuppression, are lacking. Available published studies are limited to case reports and small series often from an earlier transplant era and even from a different era of cardiac infection diagnostics. We sought to describe the clinical