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1.
Am J Transplant ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38801991

ABSTRACT

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.

2.
Int J Infect Dis ; 144: 107027, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38670483

ABSTRACT

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies. METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis was performed to evaluate the factors associated with yield. RESULTS: A total of 570 biopsies performed on 527 patients were included. A histopathologic diagnosis of osteomyelitis was made in 68.4% (359 of 525) of biopsies, and microbiological cultures were positive in 29.6% (169 of 570). Elevated erythrocyte sedimentation rate was positively associated with a histopathologic diagnosis of osteomyelitis (odds ratio [OR] =1.96, P = 0.007) and positive cultures from bone cores (OR = 1.02, P ≤0.001) and aspirate (OR = 1.02, P ≤0.001). Increased total core length was positively associated with a histopathologic diagnosis of osteomyelitis (OR = 1.81, P = 0.013) and positive cultures from bone cores (OR = 1.65, P = 0.049). Clinical management was affected by ICNB in 37.5% (214 of 570) of cases. CONCLUSIONS: In this large cohort, ICNB yielded approximately 30% positive cultures and changed clinical management in over one-third of the patients.


Subject(s)
Image-Guided Biopsy , Osteomyelitis , Humans , Osteomyelitis/diagnosis , Osteomyelitis/microbiology , Osteomyelitis/pathology , Osteomyelitis/drug therapy , Retrospective Studies , Male , Image-Guided Biopsy/methods , Female , Middle Aged , Biopsy, Large-Core Needle/methods , Aged , Adult , Aged, 80 and over , Spine/pathology , Spine/diagnostic imaging , Spine/microbiology , Spinal Diseases/diagnosis , Spinal Diseases/microbiology , Spinal Diseases/pathology , Spinal Diseases/drug therapy
3.
Open Forum Infect Dis ; 11(2): ofad662, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38352150

ABSTRACT

Background: Ceftriaxone is a convenient option for methicillin-sensitive Staphylococcus aureus (MSSA) outpatient parenteral antimicrobial therapy (OPAT), but population-based studies for its effectiveness are lacking. Methods: In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models. Results: Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61-64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01-2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81-3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18-2.23]), central line-associated BSI (aOR, 1.72 [95% CI, 1.33-2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18-2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI, .67-1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI, .66-1.10]) when compared with oxacillin/nafcillin/cefazolin. Conclusions: In this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin.

4.
Nano Lett ; 24(1): 229-237, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38146928

ABSTRACT

Rapid and accurate quantification of low-abundance protein biomarkers in biofluids can transform the diagnosis of a range of pathologies, including infectious diseases. Here, we harness ultrabright plasmonic fluors as "digital nanolabels" and demonstrate the detection and quantification of subfemtomolar concentrations of human IL-6 and SARS-CoV-2 alpha and variant proteins in clinical nasopharyngeal swab and saliva samples from COVID-19 patients. The resulting digital plasmonic fluor-linked immunosorbent assay (digital p-FLISA) enables detection of SARS-CoV-2 nucleocapsid protein, both in solution and in live virions. Digital p-FLISA outperforms the "gold standard" enzyme-linked immunosorbent assay (ELISA), having a nearly 7000-fold lower limit-of-detection, and outperforms a commercial antigen test, having over 5000-fold improvement in analytical sensitivity. Detection and quantification of very low concentrations of target proteins holds potential for early detection of pathological conditions, treatment monitoring, and personalized medicine.


Subject(s)
COVID-19 , Humans , Enzyme-Linked Immunosorbent Assay , COVID-19/diagnosis , Fluoroimmunoassay , SARS-CoV-2 , Biomarkers , Sensitivity and Specificity
5.
Nat Biomed Eng ; 7(12): 1556-1570, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36732621

ABSTRACT

Lateral-flow assays (LFAs) are rapid and inexpensive, yet they are nearly 1,000-fold less sensitive than laboratory-based tests. Here we show that plasmonically active antibody-conjugated fluorescent gold nanorods can make conventional LFAs ultrasensitive. With sample-to-answer times within 20 min, plasmonically enhanced LFAs read out via a standard benchtop fluorescence scanner attained about 30-fold improvements in dynamic range and in detection limits over 4-h-long gold-standard enzyme-linked immunosorbent assays, and achieved 95% clinical sensitivity and 100% specificity for antibodies in plasma and for antigens in nasopharyngeal swabs from individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Comparable improvements in the assay's performance can also be achieved via an inexpensive portable scanner, as we show for the detection of interleukin-6 in human serum samples and of the nucleocapsid protein of SARS-CoV-2 in nasopharyngeal samples. Plasmonically enhanced LFAs outperform standard laboratory tests in sensitivity, speed, dynamic range, ease of use and cost, and may provide advantages in point-of-care diagnostics.


Subject(s)
Immunoconjugates , Nanoparticles , Humans , SARS-CoV-2 , Enzyme-Linked Immunosorbent Assay , Antibodies , Point-of-Care Testing
6.
Curr Opin Organ Transplant ; 27(4): 235-242, 2022 08 01.
Article in English | MEDLINE | ID: mdl-36354248

ABSTRACT

PURPOSE OF REVIEW: Recipients of solid organ transplants (SOTs) suffer a significant burden of invasive fungal infections (IFIs). The emergence of drug-resistant fungi and toxicities of currently used antifungal agents as well as drug-drug interactions with immunosuppressants make their treatment challenging. This review discusses selected novel antifungal agents in the development pipeline that can currently be used through clinical trials or may be commercially available in the near future. RECENT FINDINGS: These agents in development have novel pharmacokinetics and pharmacodynamics, expanded spectra of activity and excellent safety profiles. SUMMARY: The properties of novel antifungal agents have the potential to expand the therapeutic options for IFIs in recipients of SOTs.


Subject(s)
Invasive Fungal Infections , Mycoses , Organ Transplantation , Humans , Antifungal Agents/adverse effects , Mycoses/diagnosis , Mycoses/drug therapy , Mycoses/microbiology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Transplant Recipients , Organ Transplantation/adverse effects
7.
J Clin Pharm Ther ; 47(12): 2188-2195, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36257600

ABSTRACT

INTRODUCTION: Vancomycin is commonly used during outpatient parenteral antimicrobial therapy (OPAT). Therapeutic drug monitoring (TDM) of vancomycin is recommended to ensure effective and safe therapy, as use has been associated with acute kidney injury (AKI). METHODS: The MarketScan® Commercial Database was queried from 2010 to 2016 to identify patients aged 18-64 years discharged from an inpatient hospitalization on vancomycin OPAT. The primary endpoint was hospital readmission with AKI within 6 weeks of index hospital discharge. TDM was defined as at least one vancomycin level obtained during outpatient therapy. Bivariate analysis was used to examine associations with outcomes; significant factors were incorporated into a multivariable logistic regression model. RESULTS: A total of 14,196 patients were included in the study; median age was 54 years and 53.8% were male. Readmission with AKI occurred in 385 (2.7%) and was independently associated with chronic kidney disease (aOR 2.63 [95%CI 1.96-3.52]), congestive heart failure (1.81 [1.34-2.44]), chronic liver disease (1.74 [1.17-2.59]), hypertension (1.73 [1.39-2.17]), septicemia (1.61 [1.30-2.00]), and concomitant OPAT with IV penicillins (1.73 [1.21-2.49]) while skin and soft tissue infection (0.67 [0.54-0.83]) and surgical site infection (0.74 [0.59-0.93]) were associated with lower risk of readmission with AKI. TDM was not associated with lower risk of readmission with AKI. CONCLUSION: Chronic kidney disease, congestive heart failure, hypertension, chronic liver disease, septicemia, and concomitant OPAT with IV penicillins were significantly associated with higher risk of readmission with AKI during vancomycin OPAT.


Subject(s)
Acute Kidney Injury , Anti-Infective Agents , Heart Failure , Hypertension , Renal Insufficiency, Chronic , Sepsis , Humans , Male , Middle Aged , Female , Vancomycin/adverse effects , Anti-Bacterial Agents/adverse effects , Outpatients , Patient Readmission , Prevalence , Retrospective Studies , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Risk Factors , Penicillins , Sepsis/drug therapy , Hypertension/drug therapy , Heart Failure/drug therapy , Renal Insufficiency, Chronic/chemically induced
8.
Clin Microbiol Infect ; 28(9): 1193-1202, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35339675

ABSTRACT

BACKGROUND: Antibiotic use drives antibiotic resistance. OBJECTIVES: To systematically review the literature and estimate associations between prior exposure to antibiotics across World Health Organization's (WHO) AWaRe categories (Access, Watch, Reserve) and isolation of critical and high-priority multidrug resistant organisms (MDROs) on the WHO priority pathogen list. DATA SOURCES: Embase, Ovid Medline, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (from inception to 20/08/2020). STUDY ELIGIBILITY CRITERIA: Case-control, cohort, or experimental studies that assessed the risk of infection/colonization with MDROs. PARTICIPANTS: Inpatients or outpatients of any age and sex. INTERVENTIONS: Prior exposure to antibiotics that could be categorized into the AWaRe framework. DATA ANALYSIS: Tailored design-specific checklists applied to each included study. For each antibiotic/class, crude odds ratios (ORs) were pooled through random-effects meta-analyses, both overall and by MDRO. Heterogeneity was examined. RESULTS: We identified 349 eligible studies. All were observational, prone to bias due to design and lack of adjustment for confounding, and not primarily designed to compare associations across AWaRe categories. We found statistically significant associations between prior exposure to almost all antibiotics/classes across AWaRe categories and colonization/infection with any MDRO. We observed higher ORs for Watch and Reserve antibiotics than with Access antibiotics. First generation cephalosporins (Access) had the least association with any MDRO colonization/infection (58 studies; OR = 1.2 [95% CI: 1.0-1.4]), whereas strongest associations were estimated for linezolid (Reserve) (22 studies; OR = 2.6 [95% CI: 2.1-3.1]), followed by carbapenems (Watch) (237 studies; OR = 2.3 [95% CI: 2.1-2.5]). There was high heterogeneity for all antibiotic/MDRO associations. CONCLUSIONS: Optimising use of Access antibiotics is likely to reduce the selection of MDROs and global antibiotic resistance. Despite data limitations, our study offers a strong rationale for further adoption of AWaRe as an important tool to improve antibiotic use globally.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria , Carbapenems , Cephalosporins , Electrolytes , Linezolid , World Health Organization
9.
Res Sq ; 2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35194598

ABSTRACT

Lateral flow assays (LFAs) are the cornerstone of point-of-care diagnostics. Although rapid and inexpensive, they are 1000-fold less sensitive than laboratory-based tests and cannot be used for definitive negative diagnosis. Here, we overcome this fundamental limitation by employing plasmonically-enhanced nanoscale colorimetric and fluorescent labels. Plasmonic LFAs (p-LFAs) enabled ultrasensitive detection and quantification of low abundance analytes, without compromising the direct visual detection of conventional LFAs. Dynamic ranges and limits of detection were up to 100-fold superior to "gold standard" ELISA (enzyme-linked immunosorbent assay). p-LFAs had sample-to-answer time of 20 min, compared to 4 hours for ELISA, while achieving over 95% analytical sensitivity and 100% analytical specificity for antibodies and antigens of SARS-CoV-2 in human specimens. We also demonstrate that the p-LFAs enable quantitative detection of the target analytes in a standard-free manner. p-LFAs offer potential as a broadly adaptable point-of-care diagnostic platform that outperforms standard laboratory tests in sensitivity, speed, dynamic range, ease of use, and cost.

10.
EClinicalMedicine ; 27: 100563, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33205031

ABSTRACT

BACKGROUND: Cryptococcosis is one of the most common life-threatening opportunistic mycoses worldwide. Insidious presentation and slow onset of symptoms make it difficult to recognize, complicating the diagnostic process. Delays in diagnosis may lead to increased mortality. We aim to determine the frequency of missed opportunities for diagnosis of cryptococcosis and its effects on mortality. METHODS: To estimate the proportion of individuals with a potentially missed diagnosis for cryptococcosis in hospitalized patients, we conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases from 2005 to 2015 from eight states. All hospitalized adult patients diagnosed with cryptococcal infection or cryptococcal meningitis were included. Potentially missed diagnoses were defined as admissions coded for a procedure or diagnosis suggestive of cryptococcosis in the 90-days prior to the initial cryptococcosis admission. Generalized estimating equations models were used to evaluate the association between underlying comorbidities and potential missed diagnosis of cryptococcosis and 90-day all-cause in-hospital mortality. FINDINGS: Of 5,354 patients with cryptococcosis, 2,445 (45·7%) were people living with HIV (PLWH). Among PLWH, 493/2,445 (20·2%) had a potentially missed diagnosis, of which 83/493 (16·8%) died while hospitalized compared with 265/1,952 (13·6%) of those without a potentially missed diagnosis (relative risk [RR] 1·04, 95% CI 0·99-1·09). Among HIV-negative patients, 977/2,909 (33·6%) had a potentially missed diagnosis, of which 236/977 (24·2%) died while hospitalized compared with 298/1,932 (15·4%) of those not missed (RR 1·12, 95% CI 1·07-1·16). INTERPRETATION: Missed opportunities to diagnose cryptococcosis are common despite highly efficacious diagnostic tests and are associated with increased risk of 90-day mortality in HIV-negative patients. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality. FUNDING: National Center for Advancing Translational Sciences, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.

11.
Open Forum Infect Dis ; 7(9): ofaa341, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32908944

ABSTRACT

BACKGROUND: Staphylococcus aureus bloodstream infections (BSIs) are associated with significant morbidity and mortality. Ceftriaxone is convenient for outpatient parenteral antimicrobial therapy (OPAT), but data for this indication are limited. METHODS: Adult patients with methicillin-susceptible Staphylococcus aureus (MSSA) BSI discharged on OPAT with cefazolin, oxacillin, or ceftriaxone for at least 7 days were included. We compared outcomes of ceftriaxone vs either oxacillin or cefazolin. Ninety-day all-cause mortality, readmission due to MSSA infection, and microbiological failure were examined as a composite outcome and compared among groups. Rates of antibiotic switches due to intolerance were assessed. RESULTS: Of 243 patients included, 148 (61%) were discharged on ceftriaxone and 95 (39%) were discharged on either oxacillin or cefazolin. The ceftriaxone group had lower rates of intensive care unit care, endocarditis, and shorter duration of bacteremia, but higher rates of cancer diagnoses. There was no significant difference in the composite adverse outcome in the oxacillin or cefazolin group vs the ceftriaxone group (18 [19%] vs 31 [21%]; P = .70), comprising microbiological failure (6 [6.3%] vs 9 [6.1%]; P = .94), 90-day all-cause mortality (7 [7.4%] vs 15 [10.1%]; P = .46), and readmission due to MSSA infection (10 [10.5%] vs 13 [8.8%]; P = .65). Antibiotic intolerance necessitating a change was similar between the 2 groups (4 [4.2%] vs 6 [4.1%]; P = .95). CONCLUSIONS: For patients with MSSA BSI discharged on OPAT, within the limitations of the small numbers and retrospective design we did not find a significant difference in outcomes for ceftriaxone therapy when compared with oxacillin or cefazolin therapy.

12.
J Clin Microbiol ; 58(11)2020 10 21.
Article in English | MEDLINE | ID: mdl-32848037

ABSTRACT

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH.


Subject(s)
Cryptococcosis , Cryptococcus , HIV Infections , Meningitis, Cryptococcal , Antigens, Fungal , Cryptococcosis/diagnosis , HIV Infections/complications , Humans , Latex Fixation Tests , Retrospective Studies
13.
Am J Med ; 132(8): 977-983.e1, 2019 08.
Article in English | MEDLINE | ID: mdl-31077652

ABSTRACT

BACKGROUND: Cryptococcal epidemiology is changing in the modern antiretroviral era, and immune status informs outcomes. We describe the differences in clinical presentation and mortality of cryptococcosis by immune status in the antiretroviral therapy era. METHODS: We conducted a single-center retrospective cohort study of patients diagnosed with cryptococcosis from 2002 through 2017. Data included demographics, clinical features, diagnostics, and mortality. RESULTS: We identified 304 patients with Cryptococcus neoformans infections: 105 (35%) were people living with human immunodeficiency virus (HIV), 41 (13%) had a history of transplantation, and 158 (52%) were non-HIV nontransplant (NHNT). Age analysis showed that people living with HIV were younger (40 years) than transplant (53 years) and NHNT (61 years) (P < .001). Fevers and headache were more common in people living with HIV (70% and 57%) than in transplant (49% and 29%) and NHNT (49% and 38%) (P = .003 and P = .001), respectively. Meningitis was more common in people living with HIV (68%) than in transplant recipients (32%) or NHNT (39%, P < .001). Disseminated cryptococcosis was more common in people living with HIV (97%) as compared with transplant (66%) or NHNT (73%) (P < .001). Time to diagnosis from hospitalization was longer for transplant (median 2 days, interquartile range [IQR] ± 9 days) and NHNT patients (median 2 days, IQR ± 7 days) as compared with people living with HIV (median 1 day, IQR ± 2 days) (P = .003). NHNT patients had a higher risk of 90-day mortality (hazard ratio 3.3; 95% confidence interval, 1.9-5.8) as compared with people living with HIV. CONCLUSIONS: The majority of cryptococcosis occurs in NHNT patients. NHNT patients had more localized pulmonary cryptococcosis and significantly higher 90-day mortality. Cryptococcosis in NHNT patients appears to be a distinct entity that needs further study and requires a higher level of clinical suspicion than it currently receives.


Subject(s)
Cryptococcosis/mortality , Adult , Cohort Studies , Cryptococcosis/etiology , Cryptococcus neoformans/drug effects , Cryptococcus neoformans/pathogenicity , Female , HIV Infections/complications , Humans , Male , Middle Aged , Organ Transplantation/adverse effects , Organ Transplantation/methods , Proportional Hazards Models , Retrospective Studies , Risk Factors , Statistics, Nonparametric
14.
Clin Infect Dis ; 66(4): 608-611, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29028978

ABSTRACT

In this population-based study in the contemporary era in the United States, the proportion of human immunodeficiency virus (HIV)-negative patients with cryptococcosis approaches that in HIV-infected patients. Cryptococcosis is associated with higher mortality rates in HIV-negative patients (including organ transplant recipients).


Subject(s)
Cryptococcosis/epidemiology , Cryptococcosis/mortality , HIV Infections/epidemiology , Organ Transplantation/adverse effects , Population Health , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Female , HIV Infections/complications , Humans , Male , Meningitis, Cryptococcal , Middle Aged , Retrospective Studies , Transplant Recipients , United States/epidemiology , Young Adult
17.
Open Forum Infect Dis ; 4(1): ofx004, 2017.
Article in English | MEDLINE | ID: mdl-28480277

ABSTRACT

BACKGROUND: Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT. METHODS: We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006-2012), New York (2006-2011), and California (2004-2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified. RESULTS: A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4-2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5-1816), heart (195 days; range, 4-1061), and liver (200 days; range, 4-1581) compared with kidney transplant recipients (616 days; range, 12-2393; P < .001, log rank test). Very early-onset disease (<30 days after transplantation) more frequently occurred in liver and lung transplant recipients. Lung transplant recipients had the highest risk of cryptococcosis (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.21-3.60). Cryptococcosis was associated with death (HR, 2.29; 95% CI, 1.68-3.11), after adjusting for age, type of SOT, and other comorbidities. CONCLUSIONS: Cryptococcosis is rare after SOT, but it is associated with significantly increased risk of death. Lung transplant recipients are at highest risk for cryptococcosis among SOTs. Nonkidney transplants have earlier onset of cryptococcosis and higher risk of death compared with kidney transplant recipients.

19.
Transplantation ; 100(5): 1073-8, 2016 05.
Article in English | MEDLINE | ID: mdl-26950719

ABSTRACT

BACKGROUND: Nontuberculous mycobacterial (NTM) infections have the potential to affect outcomes in solid organ transplant (SOT) recipients. METHODS: Retrospective cohort of adults who underwent SOT at a Midwestern hospital between January 1, 2004, and December 31, 2013. NTM-infected patients had at least 1 positive culture for NTM posttransplant. NTM disease was defined by 1) American Thoracic Society/Infectious Disease Society of America criteria for respiratory specimens or 2) NTM cultured from a sterile site with a compatible clinical syndrome. The remaining NTM infected patients were classified as colonized. Cox regression analysis was used to determine the association of NTM with mortality among lung transplant recipients. RESULTS: Of 3338 SOT recipients, 50 (1.5%) had NTM infection during a median 1038 days (range, 165-3706) follow-up posttransplant. Forty-three patients (86%) with NTM infection were lung transplant recipients; 18 of 43 (41.8%) were treated for NTM and 6 (13.9%) met disease criteria. Isolation of the same species on multiple occasions was associated with treatment among the colonized lung transplant recipients (8/12 [67%] vs 3/25 [12%] who were not treated, P = 0.014). NTM infection was not associated with increased mortality in lung transplant recipients (9/43 [20.9%] in infected died versus 161/510 [31.6%] in uninfected, age-adjusted hazard ratio, 0.56; 95% confidence interval, 0.2-1.1; P = 0.091). Three of 6 lung transplant recipients with NTM disease died compared with 6 of 37 colonized (hazard ratio, 7.0; 95% confidence interval, 1.5-31.5; P = 0.003). CONCLUSIONS: Among SOT patients, NTM were most frequently identified from lung transplant recipients. NTM infection was not associated with increased mortality, although NTM disease was associated with increased mortality compared with colonization in lung transplant recipients.


Subject(s)
Lung Transplantation/adverse effects , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium Infections, Nontuberculous/epidemiology , Organ Transplantation/adverse effects , Adult , Aged , Female , Follow-Up Studies , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Lung Transplantation/methods , Male , Middle Aged , Midwestern United States , Mycobacterium Infections, Nontuberculous/therapy , Organ Transplantation/methods , Proportional Hazards Models , Retrospective Studies , Risk , Time Factors , Treatment Outcome , Young Adult
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