The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Oral antivirals for COVID-19 among patients with cancer.

PURPOSE: Immunocompromised individuals, such as those diagnosed with cancer, are at a significantly higher risk for severe illness and mortality when infected with SARS-CoV-2 (COVID-19) than the general population. Two oral antiviral treatments are approved for COVID-19: Paxlovid® (nirmatrelvir/ritonavir) and Lagevrio® (molnupiravir). There is a paucity of data regarding the benefit from these antivirals among immunocompromised patients with cancer, and recent studies have questioned their efficacy among vaccinated patients, even those with risk factors for severe COVID-19. METHODS: We evaluated the efficacy and safety of nirmatrelvir/ritonavir and molnupiravir in preventing severe illness and death using our database of 457 patients with cancer and COVID-19 from Brown University-affiliated hospitals. RESULTS: Sixty-seven patients received nirmatrelvir/ritonavir or molnupiravir and were compared to 45 concurrent controls who received no antiviral treatment despite being eligible to receive it. Administration of nirmatrelvir/ritonavir or molnupiravir was associated with improved survival and lower 90-day all-cause and COVID-19-attributed mortality (p < 0.05) and with lower peak O2 requirements (ordinal odds ratio [OR] 1.52, 95% confidence interval [CI] 0.92-2.56). CONCLUSION: Acknowledging the small size of our sample as a limitation, we concluded that early antiviral treatment might be beneficial to immunocompromised individuals, particularly those with cancer, when infected with SARS-CoV-2. Larger-scale, well-stratified studies are needed in this patient population.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Cutaneous Sporothrix globosa infection mimicking cryptococcosis in a patient with history of kidney transplant.

Sporotrichosis is a subacute-to-chronic infection caused by Sporothrix species, a dimorphic fungus. Virulence varies by Sporothrix species and presentation can be region dependent. The patient had a history of immunosuppression as a result of a kidney transplant, and presented with a high disease burden on histopathological examination, but responded well to itraconazole. The case suggests considering Sporothrix speciation in immunocompromised patients to best determine treatment modality and duration.

Use of anti-spike monoclonal antibodies in kidney transplant recipients with COVID-19: Efficacy, ethnic and racial disparities.

Organ transplant recipients may not mount an adequate immune response to COVID-19 infection and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAbs), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. We identified KTR with COVID-19 between March 1, 2020 and April 30, 2021. Patients were excluded if they had multi-organ transplant or hospital-acquired COVID-19. We studied 95 KTR; 20 received mAb. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15% vs. 76%, p < 0.001). This association remained significant after adjustment for potential confounders, and analysis of mAb administration as a time-dependent variable, with day of symptom onset as day 1 (adjusted HR 0.216, p = 0.04). Black or Hispanic patients were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER. In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, have been exacerbated by the COVID-19 pandemic. Antiviral mAbs are a promising therapeutic modality, especially for immunocompromised patients.

Elevated Tacrolimus Levels at Time of Diagnosis of COVID-19 Compared to Baseline Among Hospitalized Organ Transplant Recipients.

BACKGROUND: The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied. OBJECTIVE: To study the effect of COVID-19 on tacrolimus trough levels (primary outcome) in OTRs and the association of the later with acute kidney injury, bacterial infection, and oxygen requirements. METHODS: We studied adult (>18-year-old) hospitalized OTRs with COVID-19, who were receiving tacrolimus between 3/1 and 12/16/2020. RESULTS: Among 30 OTRs, 67% were men, 90% had a kidney transplant. Median age was 60.5 (interquartile range [IQR]: 45-68) years, median time from transplant 36 (IQR: 20-84) months. Tacrolimus troughs were higher on admission for COVID-19 than baseline (average over 6 months prior) (P = .001). Eighteen patients (60%) had admission tacrolimus trough >10, 5 (17%) >20 ng/mL. Patients with diarrhea had borderline higher tacrolimus troughs, compared to those without diarrhea (P = .09). Organ transplant recipients with a tacrolimus trough >10 ng/mL were more likely to have elevated aspartate aminotransferase on admission (P = .01) and require supplemental oxygen. (P = .026). CONCLUSION AND RELEVANCE: Tacrolimus trough levels were elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. Potential mechanisms are diarrhea and hepatic involvement in COVID-19. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed; management of immunosuppression should be individualized.

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

BACKGROUND: Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. METHODS: In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FINDINGS: Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. INTERPRETATION: Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. FUNDING: American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Antibiotic use during cytarabine consolidation in acute myeloid leukemia.

Acute myeloid leukemia (AML) patients undergoing consolidation chemotherapy with intermediate or high-dose cytarabine (IDAC/HiDAC) are often placed on prophylactic antibacterials. This practice is largely based on the benefits of prophylaxis (PPX) during induction chemotherapy. However, recent concerns regarding antibacterial prophylaxis have emerged including risk of Clostridioides difficile colitis, medication toxicities, and the potential for fostering multidrug-resistant pathogens. We therefore retrospectively explored whether antibacterial PPX is beneficial during cytarabine consolidation. Adult AML patients who received IDAC/HiDAC at our institution from January 2007 to March 2018 were evaluated for receipt of antibacterial PPX. The primary endpoint was rate of febrile neutropenia (FN); secondary endpoints were rates of unplanned hospitalization, bacteremia, infection from resistant organisms, C. difficile colitis, and death from infection. One hundred twenty patients with data from 229 IDAC/HiDAC cycles were included. Patients who received antibacterial PPX were more often hospitalized during cytarabine cycle 1 (C1) than those who received no PPX. Patients who received PPX had significantly more episodes of bacteremia, in addition to infections from resistant, predominantly Gram-positive organisms during cycle 1 of consolidation than those without PPX. Antibacterial PPX during IDAC/HiDAC consolidation treatment at our institution did not decrease the rates of FN, hospitalization, or bacteremia and was associated with higher risk of infection from drug-resistant bacteria in C1. Prospective studies examining antibacterial prophylaxis during cytarabine consolidation for AML patients are necessary, with strong consideration made for institution-specific protocols.

A eulogy for Dr Francisco Miguel Marty Forero.

As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being.

Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID-19 who recovered after receiving COVID-19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.

Antifungal prophylaxis during 7 + 3 induction chemotherapy for acute myeloid leukemia is associated with improved survival, in a setting with low incidence of invasive mold infections.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myeloid leukemia (AML). In this patient population, antifungal prophylaxis (AP) has been associated with decreased incidence of IFIs and better survival. However, some centers have not adopted AP during induction chemotherapy for AML, as it is unclear whether AP improves outcomes in settings where the incidence of invasive mold infections is low. We retrospectively assessed the differences in clinical outcomes and resource utilization in patients undergoing 7 + 3 induction chemotherapy for AML, after implementing a policy of AP as part of a dedicated inpatient malignant hematology service (HS) at Rhode Island Hospital. Between January 1, 2007 and April 1, 2019, 56 patients with AML received AP during 7 + 3 induction chemotherapy and 52 patients did not, without significant differences in their baseline characteristics. Use of AP was associated with less proven or probable IFI (0% vs. 6%, P = 0.1) and lower all-cause in-hospital mortality (7% vs. 21%, P < 0.05), without significant increases in resource utilization or toxicities. Empiric and targeted antifungal therapies were more frequently started in the non-AP group (69%) than changed in the AP group (41%, P < 0.005). Having a dedicated inpatient malignant hematology service was also associated with improved outcomes. However, use of AP was associated with better survival (30-day post-induction survival log-rank P < 0.05), prior to the implementation of this clinical service as well, which is suggestive of an independent benefit from AP.

Validation of pneumonia prognostic scores in a statewide cohort of hospitalised patients with COVID-19.

OBJECTIVE: We aimed to externally validate the predictive performance of two recently developed COVID-19-specific prognostic tools, the COVID-GRAM and CALL scores, and prior prognostic scores for community-acquired pneumonia (CURB-65), viral pneumonia (MuBLSTA) and H1N1 influenza pneumonia (Influenza risk score) in a contemporary US cohort. METHODS: We included 257 hospitalised patients with laboratory-confirmed COVID-19 pneumonia from three teaching hospitals in Rhode Island. We extracted data from within the first 24 hours of admission. Variables were excluded if values were missing in >20% of cases, otherwise, missing values were imputed. One hundred and fifteen patients with complete data after imputation were used for the primary analysis. Sensitivity analysis was performed after the exclusion of one variable (LDH) in the complete dataset (n = 257). Primary and secondary outcomes were in-hospital mortality and critical illness (mechanical ventilation or death), respectively. RESULTS: Only the areas under the receiver-operating characteristic curves (RO-AUC) of COVID-GRAM (RO-AUC = 0.775, 95% CI 0.525-0.915) for in-hospital death, and CURB65 for in-hospital death (RO-AUC = 0.842, 95% CI 0.674-0.932) or critical illness (RO-AUC = 0.766, 95% CI 0.584-0.884) were significantly better than random. Sensitivity analysis yielded similar trends. Calibration plots showed better agreement between the estimated and observed probability of in-hospital death for CURB65, compared with COVID-GRAM. The negative predictive value (NPV) of CURB65 ≥2 was 97.2% for in-hospital death and 88.1% for critical illness. CONCLUSIONS: The COVID-GRAM score demonstrated acceptable predictive performance for in-hospital death. The CURB65 score had better prognostic utility for in-hospital death and critical illness. The high NPV of CURB65 values ≥2 may be useful in triaging and allocation of resources.

Correction to: Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

After publication of the original article [1], we were notified that an author's family name has been erroneously spelled. Aditya Chandrokar should be replaced with Aditya Chandorkar.

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. METHODS: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. RESULTS: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%). CONCLUSIONS: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

Hyperammonemia syndrome due to Ureaplasma urealyticum in a kidney transplant recipient: A case of disseminated disease from a fluoroquinolone-resistant isolate.

Ureaplasma species (spp.) are common colonizers of the urogenital tract but may cause systemic infection in immunocompromised patients. They release significant amounts of ammonia via urea hydrolysis and have been recently implicated in the pathogenesis of hyperammonemia syndrome after organ transplantation. We describe a unique case of hyperammonemia syndrome after kidney transplant caused by U urealyticum infection, and the first, to our knowledge, case of a fluoroquinolone-resistant Ureaplasma strain causing hyperammonemia syndrome. A 17-year-old female developed intermittent fevers, rising creatinine, sterile pyuria and debilitating polyarthritis approximately 1 year after kidney transplant. Serum ammonia level was elevated, and urine PCR was positive for U urealyticum. Near the end of treatment with levofloxacin, she had rebound hyperammonemia, which preceded clinical relapse of polyarthritis and encephalopathy. Blood and urine PCR and synovial fluid culture were positive for U urealyticum. Susceptibility testing showed fluoroquinolone resistance, but she responded well to azithromycin and doxycycline. The frequency of Ureaplasma spp. infection in immunocompromised patients is probably underestimated due to diagnostic challenges. Ammonia levels were helpful biomarkers of response to antimicrobial therapy in our case. Susceptibility testing of clinical isolates should be pursued. In serious Ureaplasma spp. infections, particularly in immunocompromised patients, two empiric antibiotics may be indicated given the potential for antimicrobial resistance.

Increased Risk of Infectious Complications in Older Patients With Indolent Non-Hodgkin Lymphoma Exposed to Bendamustine.

Background: Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL. Methods: For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenström macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine. Results: Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure. Conclusions: Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.

False positive bronchoalveolar lavage galactomannan: Effect of host and cut-off value.

OBJECTIVES: Bronchoalveolar lavage galactomannan (BAL-GM) is a mycological criterion for diagnosis of probable invasive aspergillosis (IA) per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORT-MSG) consensus criteria, but its real-world positive predictive value (PPV) has not been well-studied. Our aim was to estimate the PPV of BAL-GM in a contemporary cohort of patients with positive BAL-GM. METHODS: We identified consecutive patients with ≥1 positive BAL-GM value (index ≥ 0.5) at Brigham and Women's Hospital from 11/2009 to 3/2016. We classified patients as having no, possible, probable, or proven IA, excluding BAL-GM as mycological criterion. RESULTS: We studied 134 patients: 54% had hematologic malignancy (HM), and 10% were solid organ transplant (SOT) recipients. A total of 42% of positive (≥0.5) BAL-GM results were falsely positive (PPV 58%). The number of probable IA cases was increased by 23% using positive BAL-GM as mycologic criterion alone. PPV was higher in patients with HM or SOT (P < 0.001) and with use of higher thresholds for positivity (BAL-GM ≥ 1 vs 1-0.8 vs 0.8-0.5: P = 0.002). CONCLUSIONS: 42% of positive BAL-GM values were falsely positive. We propose a critical reassessment of BAL-GM cutoff values in different patient populations. Accurate noninvasive tests for diagnosis of IA are urgently needed.

Brucellosis in Adults and Children: A 10-Year Case Series at Two Large Academic Hospitals in Houston, Texas.

OBJECTIVES: Brucellosis is one of the most common zoonoses worldwide. Most cases in the United States occur among travelers or immigrants from endemic regions, mostly Central America. In this study, we aimed at describing and comparing the epidemiology and clinical presentation of brucellosis in pediatric and adult patients at two large tertiary care centers in Houston, Texas. METHODS: We identified patients diagnosed as having brucellosis between January 2000 and December 2009 by searching electronic medical records and reviewing microbiology records for positive cultures. Cases were defined as those with a positive blood culture for Brucella sp, a serum agglutination titer ≥1:80 (or both positive blood culture and serum agglutination titer ≥1:80), along with an epidemiologic risk factor and clinical presentation that is consistent with brucellosis. RESULTS: Six adult and 12 pediatric cases were identified; 13 of 18 (72%) cases were immigrants, mostly from Central America. The median ages for adult and pediatric patients were 53 and 3 years old, respectively. Ingestion of unpasteurized milk products was frequently reported. Common clinical features included fever (83%), arthralgias or arthritis (67%), and hepatosplenomegaly (61%). Positive blood cultures were more frequently reported among children than adults (83% vs 33%, P = 0.03). The most common laboratory finding was mildly elevated transaminases. Three adults (50%) but no children developed thrombocytopenia (P = 0.02). Relapsed infection was a frequent occurrence. CONCLUSIONS: In the southern United States, brucellosis is an important consideration in the differential diagnosis of immigrants presenting with undifferentiated fever and joint complaints. A careful history often reveals an epidemiologic risk factor such as ingestion of unpasteurized dairy products.

Candidemia in Adults at a Tertiary Hospital in China: Clinical Characteristics, Species Distribution, Resistance, and Outcomes.

BACKGROUND: Candidemia is one of the most common nosocomial bloodstream infections. Early diagnosis and antifungal treatment improve clinical outcomes in some studies but not all, with diverse data reported from different institutions. Similarly, antifungal resistance is more common in the USA than in Europe, but there is little data regarding the microbiology and clinical course of candidemia in adult patients in Asia. AIMS: (1) To capture species distribution and drug resistance rates among Candida bloodstream isolates, (2) to describe clinical features of candidemia, and (3) to identify factors associated with all-cause mortality, with emphasis on early initiation of antifungal treatment, at a large tertiary University Hospital in China. METHODS: In this single-center retrospective study, we identified all patients with candidemia, between 2008 and 2014. Demographic and clinical characteristics, microbiological information, details of antifungal therapy and clinical outcomes were collected. RESULTS: We studied 166 patients. 71 (42.8%) had cancer. Candida albicans was the most frequent species (37.3%), followed by C. parapsilosis (24.1%), C. tropicalis (22.8%), and C. glabrata (14.5%). Antifungal resistance was more frequent in non-albicans strains and especially C. glabrata. Twenty patients received inappropriate treatment with all-cause mortality of 35%. The remaining 146 patients had significantly lower mortality (21.9%, P = 0.045). Among patients who received antifungal treatment, mortality rate increased with time to appropriate antifungal therapy (AAT): 13.7%, for < 24 h, 21.1% for 24-48 h, 23.1% for > 48 h, and 32.4% among patients who received no AT (χ2 for trend P = 0.039). Initiating AAT more than 24 h after blood culture collection was an independent risk factor for mortality, after adjustment for other confounders (OR 7.1, 95% CI 1.3-39.4, P = 0.024). CONCLUSIONS: Candida albicans was the most frequent cause of candidemia at a large tertiary hospital in China, but antifungal resistance is a growing concern among non-albicans Candida species. The mortality rate of patients treated with ineffective antifungal agents based on in vitro susceptibilities was similar to that of patients who received no treatment at all, and delayed initiation of antifungal treatment was associated with increased risk of death.