Clinical Characteristics and Outcomes of Endemic Mycoses After Solid Organ Transplantation: A Comprehensive Review.

Background: Geographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation, and outcomes of 5 endemic mycoses in SOT recipients. Methods: Multiple databases were reviewed from inception through May 2023 using key words for endemic fungi (eg, coccidioidomycosis or Coccidioides, histoplasmosis or Histoplasma, etc). We included adult SOT recipients and publications in English or with English translation. Results: Among 16 cohort studies that reported on blastomycosis (n = 3), coccidioidomycosis (n = 5), histoplasmosis (n = 4), and various endemic mycoses (n = 4), the incidence rates varied, as follows: coccidioidomycosis, 1.2%-5.8%; blastomycosis, 0.14%-0.99%; and histoplasmosis, 0.4%-1.1%. There were 204 reports describing 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis cases. The majority of patients were male (176 of 261 [67.4%]). Transplanted allografts were mostly kidney (192 of 268 [71.6%]), followed by liver (n = 39 [14.6%]), heart (n = 18 [6.7%]), lung (n = 13 [4.9%]), and combined kidney-liver and kidney-pancreas (n = 6 [2.7%]). In all 5 endemic mycoses, most patients presented with fever (162 of 232 [69.8%]) and disseminated disease (179 of 268 [66.8%]). Cytopenias were frequently reported for histoplasmosis (71 of 91 [78.0%]), coccidioidomycosis (8 of 11 [72.7%]) and talaromycosis (7 of 8 [87.5%]). Graft loss was reported in 12 of 136 patients (8.8%). Death from all-causes was reported in 71 of 267 (26.6%); half of the deaths (n = 34 [50%]) were related to the underlying mycoses. Conclusions: Endemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high all-cause mortality rate, including many deaths that were attributed to endemic mycoses.

Outcomes of Kidney Transplantation Among COVID-19 Recovered Patients in a Single Transplant Center.

BACKGROUND: The COVID-19 pandemic significantly lowered kidney transplantation (KT) rates worldwide, and studies regarding outcomes of patients who developed COVID-19 infection before KT are limited, especially in low to middle-income countries. BACKGROUND: To determine the 1-year graft and patient survival of kidney transplant recipients who recovered from COVID-19 infection before KT. METHODS: We retrospectively reviewed all adult end-stage renal disease patients who underwent KT at the National Kidney and Transplant Institute from June 2020 through October 2021. Transplant parameters, graft and patient survival, pretransplant COVID-19 infection, and post-KT infectious complications were recorded. Data was analyzed using two-tailed descriptive statistical tests. RESULTS: Of the 219 recipients, 23 (11%) had COVID-19 infection within 1 to 16 months before KT. The mean age of KT recipients was 36 years (range, 25-57), and 61.9% had chronic glomerulonephritis as primary renal disease. The mean duration from COVID-19 recovery to KT was 79 days (range, 21-207). There was no significant difference in the 1-year biopsy-proven acute rejection in the 2 groups, at 4.5% vs 12.5% for the COVID-19 and non-COVID-19 group, respectively. Both the 1-year graft and patient survival were similar in the COVID-19 and non-COVID-19 groups at 98.4% vs 100% and 100% vs 98.44%, respectively. CONCLUSION: There was no significant difference in biopsy-proven acute rejection, 1-year graft, and patient survival among patients who had a prior COVID-19 infection vs those who did not. Kidney transplantation appears safe when performed at least 1 month from COVID-19 infection.

Donor-derived endemic mycoses after solid organ transplantation: A review of reported cases.

BACKGROUND: Donor-derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor-derived infections (DDI) were included. RESULTS: Twenty-four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor-derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2-35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4-48) months after transplantation. The single reported possible donor-derived talaromycosis occurred in a man whose organ donor had at-risk travel to Southeast Asia. Collectively, the majority of donors had high-risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor-derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%). CONCLUSION: Donor-derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

Multidrug-resistant VAP before and during the COVID-19 pandemic among hospitalized patients in a tertiary private hospital.

Background: There is limited data on ventilator-associated pneumonia (VAP) and multidrug-resistant VAP (MDR VAP) among COVID-19 patients. Methods: A retrospective study in a single, tertiary, private hospital in the Philippines was conducted comparing the incidence, profile, and patient outcomes of MDR VAP during the pre-COVID-19 (2018-2019) and COVID-19 (2020-2021) periods. Results: In total, 80/362 (22%) patients developed VAP, 27/204 (33.75%) from pre-COVID-19 and 53/158 (66.25%) from the COVID-19 period, respectively. The majority were male [20/27 (74%) vs 34/53 (64%)], with a median age of 66 (range 35-90) and 67 (range 32-92) years in each period, respectively. Comorbidities were similar, except cardiovascular disease (14/27 vs 11/53 patients, p-value 0.005) and chronic lung disease (14/27 vs 9/53 patients, p-value 0.0012). VAP incidence density was 19.3/1000 and 27.8/1000 ventilator days (p-value 0.9819)]; median length of stay before VAP for pre- and COVID-19 periods was 17 and 10 days, respectively (p-value <0.0001). Extended-spectrum ß lactamase (ESBL)-producing resistance increased significantly [1/27 (3.7%) pre-COVID-19 vs 15/53 (28.3%)] during COVID-19, while Carbapenem-resistant Enterobacteriaceae resistance was higher in the pre-COVID-19 period (15/27 [56%] vs 10/53 [19%]). Mortality was high in both periods at 93% and 83%, respectively. On multivariate analysis, only female gender was associated with MDR VAP in the COVID-19 period (OR =3.47, [CI 1.019, 11.824], p-value < 0.047). Conclusion: The frequency of VAP and MDR VAP increased during the COVID-19 period, despite a shorter duration of hospital stay. The mortality of VAP was extremely high. Factors associated with increased risk of VAP and COVID-19 need to be studied further, and preventive measures should be prioritized.

A review of endemic mycoses after hematopoietic stem cell transplantation.

BACKGROUND: Endemic mycoses after hematopoietic stem cell transplantation (HSCT) are rarely reported. We aimed to comprehensively review the clinical presentation and outcomes of endemic mycoses in this immunocompromised population. METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as keywords (e.g., coccidioides, histoplasma, blastomyces, talaromyces, and paracoccidioides). Only hematopoietic transplants were included. RESULTS: There were 16 publications on endemic mycoses after HSCT that reported nine unique cases of histoplasmosis, seven coccidioidomycosis, and two talaromycosis. No cases of paracoccidioides and blastomycoses were identified. Fifteen cases were allogeneic hematopoietic transplant recipients and three were autologous. Many were male (14/18, 77.8%) and overall median age was 50 (range 21-75) years. Among the 16 patients with coccidiodomycosis or histoplasmosis, fever, cytopenias and disseminated disease were the most common clinical presentations, with median onset of 8 or 12 months after HSCT, respectively. Likewise, the two HSCT patients with talaromycosis presented with disseminated disease at 12 and 48 months after transplantation. The vast majority were not on effective azole prophylaxis at the time of presentation, and many had recent intensification of immunosuppression. Nine of 18 patients died (50%), and all deaths occurred among patients with disseminated endemic mycoses. CONCLUSION: Endemic mycoses among HSCT are uncommon. Onset was late, after discontinuation of azole prophylaxis, or was associated with intensification of immunosuppression. Disseminated disease was a common presentation, manifested by fever and cytopenias. Attributable mortality was high, and emphasizes the need for a high index of clinical suspicion so that prompt diagnosis and treatment is provided.

Multi-drug resistant and rifampin-resistant tuberculosis in transplant recipients.

BACKGROUND: Management of multidrug-resistant (MDR) and rifampin-resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR-TB/RR-TB treatment in transplant recipients. METHODS: Multiple databases from inception to 12/2022 were reviewed using the keywords "drug-resistant TB" or "drug-resistant tuberculosis" or "multidrug-resistant TB" or "multidrug-resistant tuberculosis". MDR-TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient-level data and reports which did not describe treatment and/or outcomes for MDR-TB were excluded. RESULTS: A total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR-TB and one was RR-TB. Seven recipients were male. The median age was 41.5 (range 16-60) years. Pre-transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high-burden countries. Seven patients were initially treated with the quadruple first-line anti-TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow-up. CONCLUSIONS: MDR-TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy.

Global Online Interest in HIV/AIDS care Services in the time of COVID-19: A Google Trends Analysis.

The Covid-19 pandemic has compounded the challenge of HIV/AIDS elimination, creating difficulties in accessing HIV care services such as early testing and treatment. This paper characterized the global online interest in HIV care services-related search terms before and during the pandemic. Global online search interest for HIV was measured using the Google Trends™ database. Spearman's rank-order correlation correlated country-specific characteristics and HIV prevalence data with the search volume index (SVI). We found a significant decrease in the global online search interest for HIV/AIDS care services-related search terms during the Covid-19 pandemic. The top countries with the highest online interest for "HIV/AIDS" search terms were Zambia, Eswatini, Malawi, Lesotho, and Zimbabwe. In addition, search volume indices for HIV correlated positively with HIV prevalence and negatively with GDP, GDP per capita, and the number of physicians. This result highlights that resource-poor countries with a high prevalence of HIV have a high online interest in HIV/AIDS. Therefore, there is a need to improve internet access, the quality of HIV-related health information, and online health literacy to improve health-seeking behavior, especially in areas with a high disease burden. Overall, our study shows that the infodemiologic approach through Google Trends™ can be used to assess the online interest of the public toward HIV infection and related healthcare services.

The hematologic profile of Filipino HIV-infected individuals and its association with CD4 counts

ABSTRACT Introduction: Hematologic abnormalities are common in HIV and involve all blood cell lineages. A study on cytopenias, as correlated with disease progression, can be valuable in resource-limited settings. This study aimed to determine the hematologic profile of HIV patients and its association with CD4 count and antiretroviral (ARV) treatment. Methods: This is a retrospective cohort study involving adult Filipino HIV patients with complete blood count (CBC) and CD4 count determinations prior to the initiation of ARV treatment and after ≥6 months of ARV treatment. Logistic regression was performed to determine the association between cytopenias and a CD4 count <200 cells/μL. Results: The study included 302 patients. Anemia was the most common cytopenia. Anemia and leukopenia were associated with an increased likelihood of having a CD4 count <200 cells/μL in ARV-naïve patients. In ARV-treated patients, leukopenia was associated with an increased probability of having a CD4 count <200 cells/μL. An increase in hemoglobin, white blood cell (WBC) and platelet counts was observed after ≥6 months of ARV treatment. Conclusion: Anemia and leukopenia can be used as markers of immune status in HIV-infected individuals and improvement in the CBC parameters can be used to assess response to ARV treatment. Routine monitoring of hematologic parameters is recommended.

A comprehensive review of Strongyloides stercoralis infection after solid organ and hematopoietic stem cell transplantation.

BACKGROUND: We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation. METHODS: CINAHL, PUBMED, and OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation. RESULTS: Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14-417) and 8.8 (range, 0-208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 [79.6%]), while skin rash (22/108 [20.3%]) and fever (31/103 [30%]) were less common. Peripheral eosinophilia was observed in half of patients (41/77 [53.2%]). Bacteremia (31/59 [52.5%]) was frequently due to Gram-negative organisms (24/31 [77.4%]). Abnormal chest radiologic findings were reported in half (56/108 [51.9%]). The majority had hyperinfection syndrome (97/108 [89.8%]) while disseminated strongyloidiasis was less common (11/108 [10.2%]). Thirty-two cases were categorized as donor-derived infection (DDI), with donors (23/24 [95.8%]) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5-34.3 weeks) after transplantation. Treatment consisted of ivermectin (n = 26), a benzimidazole (n = 27), or both drugs (n = 28). There was high all-cause mortality (48/107, 44.9%) and a high Strongyloides-attributable mortality (32/49, 65.3%). CONCLUSIONS: Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro-active screening is needed, to ensure preventive measures are provided to recipients at increased risk.

Predictors of mortality among inpatients with COVID-19 infection in a tertiary referral center in the Philippines.

Objectives: The aim of this study was to determine the predictors of mortality and describe laboratory trends among adults with confirmed COVID-19. Methods: The medical records of adult patients admitted to a referral hospital with COVID-19 were retrospectively reviewed. Demographic and clinical characteristics, and laboratory parameters, were compared between survivors and non-survivors. Predictors of mortality were determined by multivariate analysis. Mean laboratory values were plotted across illness duration. Results: Of 1215 patients, 203 (16.7%) had mild, 488 (40.2%) moderate, 183 (15.1%) severe, and 341 (28.1%) critical COVID-19 on admission. In-hospital mortality was 18.2% (0% mild, 6.1% moderate, 15.8% severe, 47.5% critical). Predictors of mortality were age ≥ 60 years, COPD, qSOFA score ≥ 2, WBC > 10 × 109/L, absolute lymphocyte count < 1000, neutrophil ≥ 70%, PaO2/FiO2 ratio ≤ 200, eGFR < 90 mL/min/1.73 m2, LDH > 600 U/L, and CRP > 12 mg/L. Non-survivors exhibited an increase in LDH and decreases in PaO2/FiO2 ratio and eGFR during the 2nd-3rd week of illness. Conclusion: The overall mortality rate was high. Predictors of mortality were similar to those of other reports globally. Marked inflammation and worsening pulmonary and renal function were evident among non-survivors by the 2nd-3rd week of illness.

Clinical characteristics of patients with asymptomatic and symptomatic COVID-19 admitted to a tertiary referral centre in the Philippines.

Objectives: To describe the clinical profile and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) across the spectrum of disease severity. Methods: This retrospective study included adult patients with confirmed COVID-19 infection admitted to a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease severity categories. Results: Of 1500 patients with COVID-19, 14.8% were asymptomatic, 13.5% had mild disease, 36.6% had moderate disease, 12.3% had severe disease and 22.7% had critical disease. Asymptomatic patients were admitted for a concurrent condition or for isolation. Patients aged >60 years, male gender and with co-morbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastrointestinal symptoms and decreased sensorium were more common in patients with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. The overall mortality rate was 15.1%. Adopting a symptom-based strategy reduced the length of hospitalization from a median of 13 [interquartile range (IQR) 7-21] days to 9 (IQR 5-14) days. Conclusion: The clinical profile and outcomes for this cohort of patients with COVID-19 was consistent with published reports. Asymptomatic infection was common, and universal testing may be a valuable strategy in the correct context, given the implications for infection control. A symptom-based strategy was found to reduce the length of hospitalization considerably.

The hematologic profile of Filipino HIV-infected individuals and its association with CD4 counts.

INTRODUCTION: Hematologic abnormalities are common in HIV and involve all blood cell lineages. A study on cytopenias, as correlated with disease progression, can be valuable in resource-limited settings. This study aimed to determine the hematologic profile of HIV patients and its association with CD4 count and antiretroviral (ARV) treatment. METHODS: This is a retrospective cohort study involving adult Filipino HIV patients with complete blood count (CBC) and CD4 count determinations prior to the initiation of ARV treatment and after ≥6 months of ARV treatment. Logistic regression was performed to determine the association between cytopenias and a CD4 count <200 cells/µL. RESULTS: The study included 302 patients. Anemia was the most common cytopenia. Anemia and leukopenia were associated with an increased likelihood of having a CD4 count <200 cells/µL in ARV-naïve patients. In ARV-treated patients, leukopenia was associated with an increased probability of having a CD4 count <200 cells/µL. An increase in hemoglobin, white blood cell (WBC) and platelet counts was observed after ≥6 months of ARV treatment. CONCLUSION: Anemia and leukopenia can be used as markers of immune status in HIV-infected individuals and improvement in the CBC parameters can be used to assess response to ARV treatment. Routine monitoring of hematologic parameters is recommended.

Association of mycoplasma with prostate cancer: A systematic review and meta-analysis.

Mycoplasmas are emerging sexually transmitted pathogens usually associated with male urinary tract infection, non-gonococcal urethritis (NGU), infertility, and prostate cancer. In this study, we review the evidence linking mycoplasma infection and prostate cancer. We conducted a systematic review and meta-analysis based on PRISMA guidelines. Four electronic databases were reviewed through January 31, 2021. Studies were eligible for inclusion if odds ratio for prevalence or incidence of colonization and/or infection were provided or calculable. All included studies were evaluated independently by three reviewers. The quality of the included studies was assessed using the Newcastle-Ottawa Scale for Case-Control Studies. Statistical analysis was done using Review Manager Version 5.4. A total of 183/744 (24.6 %) patients with prostate cancer compared to 87/495 (17.58 %) patients with benign prostatic hyperplasia (BPH) tested positive for Mycoplasma spp., while 86/666 (12.91 %) and 11/388 (2.84 %) prostate cancer patients and BPH patients, respectively, had Ureaplasma spp. infections. This meta-analysis showed that prostate cancer patients had 2.24 times higher odds (p = 0.0005) of being colonized with any species of Mycoplasma spp. and 3.6 times increased odds (p = 0.008) of being colonized with any species of Ureaplasma spp. In conclusion, patients with prostate cancer were more likely to be colonized with Mycoplasma spp. or Ureaplasma spp. compared to patients with BPH, which highlights the potential association between chronic infection and cancer. However, more studies are needed to determine the specific role that mycoplasma plays in the pathogenesis of prostate cancer.

Hyperammonemia syndrome associated with Ureaplasma spp. Infections in immunocompromised patients and transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Hyperammonemia syndrome (HS) is reported to occur in patients with Ureaplasma spp. infections. We performed a systematic review and meta-analysis of studies reporting HS in patients with Ureaplasma spp. infection. METHODS: We searched several databases (CINAHL, OVID, ProQuest, and Scopus) from inception to January 2021. We described case reports and series, and performed a meta-analysis for all cohort studies. The pooled risk ratio (RR) for the association between HS and Ureaplasma spp. infections was derived using a random-effects model. RESULTS: The systematic review yielded 18 studies. HS was reported in 53 patients with Ureaplasma spp. infections. The most common clinical manifestations were neurologic. Meta-analysis showed a higher incidence of HS (41.67%) and peak ammonia concentration among Ureaplasma spp.-infected lung transplant recipients compared with Ureaplasma spp.-negative recipients (2.84%). The risk of HS was significantly increased in Ureaplasma spp.-infected recipients compared with Ureaplasma spp.-negative recipients (RR: 14.64; CI: 2.85-75.24). Mortality from Ureaplasma-associated HS was 27.27% compared with 5.24% in those with HS from other causes. CONCLUSIONS: The risk of developing HS is higher among Ureaplasma-infected patients compared with uninfected patients. Lung transplant recipients appear to be disproportionally affected, and HS should be suspected in those who present with neurologic symptoms.

A Review of Clostridioides difficile Infection and Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea and Clostridioides difficile infection (CDI) occur frequently among adults. The pathophysiology of CDI is related to disruption of normal gut flora and risk factors include hospitalization, use of antibiotic therapy, and older age. Clinical manifestations can range from mild disease to toxic megacolon. Diagnosis is challenging and is based on a combination of clinical symptoms and diagnostic tests. Therapy includes cessation of antibiotics, or use of other agents depending on the severity of illness. Many novel agents for the treatment and prevention of CDI show promise and are under investigation.

The clinical profile and outcomes of adult patients given intravenous colistin for multidrug-resistant gram negative infections in a Philippine tertiary hospital.

OBJECTIVES: Colistimethate sodium (colistin) is used to treat multidrug-resistant gram negative infections. We describe the profile and outcomes of patients given colistin in a tertiary level government hospital in Manila, Philippines. METHODS: We performed a retrospective study of adult patients given intravenous colistin between January 2015 to June 2018 in the Philippine General Hospital. We defined clinical success as a composite of hemodynamic stability, quick Sequential Organ Failure Assessment (qSOFA) score, and microbiological cure. RESULTS: 250 patients were included, half (49.2%) were admitted in the ICU. Median age was 55 years. There was an increase in qSOFA, APACHE II score, and septic shock from baseline to 24 h prior to colistin use. Most patients had pneumonia (90.8%) with extensively drug-resistant Acinetobacter baumannii as the most common isolate (78.8%). Colistin was given in combination with meropenem (96.4%) for a median of 12 days. Nephrotoxicity was seen in 30.8%, with renal replacement therapy needed in 6%. Clinical success was seen in 61.2% of patients and overall mortality was 41.6%. CONCLUSION: Colistin was frequently used in combination with a carbapenem for treatment of XDR-related respiratory infections. Nephrotoxicity was a common adverse effect. Clinical success was modest and overall mortality was high.

The D-index is not correlated with invasive fungal infection during the early-post engraftment phase among allogeneic hematopoietic stem cell transplant recipients.

The D-index assesses neutropenia dynamics. Prolonged neutropenia is a major risk for invasive fungal infection (IFI); we hypothesized that D-index is predictive of IFI risk. We retrospectively reviewed 789 adults who underwent allogeneic hematopoietic transplant (HSCT) from 1/1/2005 to 9/30/2015. Medical records were reviewed from transplant (D0) through Day 100. The D-index was calculated as area over the neutrophil curve until engraftment. 714 patients were included for analysis. Sixteen (2%) developed probable (11) or proven (5) IFI. Median time to IFI was 40 days (range 8-98) after HSCT. Groups with and without IFI did not differ significantly in duration of mild or profound neutropenia. Median D-index of those with IFI was 4293 days neutrophil/µl compared to 3590 days neutrophil/µl for those without IFI (P = 0.17). Patients who were neutropenic on D0 showed higher rates of IFI than those who were not (10/123 [8%] vs 6/591 [1%]; P < 0.001). Only 2% developed IFI, likely due to mold-active antifungal prophylaxis. The D-index was not significantly higher in those with IFI. Duration of profound neutropenia and neutropenia at D0 may be better markers for IFI among HSCT recipients during the first 30 and 100 days after transplant.

Treatment of latent TB Infection and the risk of tuberculosis after solid organ transplantation: Comprehensive review.

BACKGROUND: Mycobacterium tuberculosis disease may occur after treatment of latent TB infection (LTBI). Prompted by a case of reactivation TB disease in a solid organ transplant (SOT) recipient who received LTBI treatment, we reviewed the literature to examine outcomes, adverse effects, resistance, and treatment choices of tuberculosis after LTBI therapy. METHODS: MEDLINE and Web of Science from inception to 5/2019 were reviewed using key words "latent tuberculosis infection" and "SOT" or "transplantation." The search yielded nine cases, 41 cohort studies and six randomized controlled trials (RCT). RESULTS: Cohort and RCT demonstrated significant reduction in TB disease among transplanted patients who received LTBI therapy; only 56/2651 (2.1%) SOT patients developed TB after LTBI therapy. Adverse drug reactions occurred in 149/1148 (12.9%) and 73/641 (11.4%) of cohort and RCT patients, respectively. Among liver recipients, 56/266 (21%) developed side effects, of which half (29/56, 51.8%) was INH-related. There was no reported INH resistance. CONCLUSIONS: Latent TB infection treatment is efficacious in SOT recipients at risk of TB disease. However, tuberculosis may still occur despite LTBI treatment. Hepatotoxicity associated with LTBI therapy is infrequent, although more commonly observed among liver recipients.

An update on Mycobacterium tuberculosis infection after hematopoietic stem cell transplantation in adults.

BACKGROUND: Mycobacterium tuberculosis (TB) is common worldwide, but is rarely reported after hematopoietic transplantation (HSCT). We reviewed all TB cases among HSCT since 2010 to provide an update on its epidemiology, clinical presentation, management and outcome. METHODS: Several databases were reviewed from January 1, 2010 to June 30, 2018 using key words tuberculosis and hematopoietic transplantation. RESULTS: The 47 cases of TB were reported during the study period. The highest TB frequency was reported from India (2.9%), with a median frequency of 2% (range, 0.18%-2.9%). The majority were recipients of allogeneic transplants (45/47, 95.7%). Pulmonary TB was the most common clinical presentation (20/47, 42.6%). The median time to clinical presentation was 4.6 (range, 3-12.9) and 2.4 (range, 0.6-5) months, based on cohort data and case reports, respectively. Fever was reported in 87.5% (14/16) of patients. First-line quadruple drug therapy was frequently used (29/35, 82.9%), with a median length of 12 and 9 months for cohorts and case reports, respectively. All-cause and attributable mortality was 27.6% (13/47), and 8.5% (4/47), respectively. CONCLUSIONS: Mycobacterium tuberculosis presents early after HSCT, most commonly as fever. A high index of suspicion is needed for early diagnosis and treatment, to prevent TB-attributable mortality.

Mycobacterium tuberculosis after solid organ transplantation: A review of more than 2000 cases.

BACKGROUND: Mycobacterium tuberculosis (TB) is a common pathogen worldwide, and it may cause significant infection after solid organ transplantation (SOT). We reviewed all reported TB cases to provide an update on its epidemiology, clinical presentation, management, and outcome after SOT. METHODS: MEDLINE, EMBASE, and OVID were reviewed from January 1, 1998, to December 31, 2016, using keywords tuberculosis and solid organ transplant or transplantation. RESULTS: There were 187 publications reporting 2082 cases of TB among kidney (n = 1719), liver (n = 253), heart (n = 77), lung (n = 25), and kidney-pancreas (n = 8) recipients. Among cohort studies, the median incidence was 2.37% (range, 0.05%-13.27%) overall. Most TB disease was considered reactivation of latent infection, occurring beyond the first year after SOT. Early-onset cases were seen among donor-derived TB cases. Fever was the most common symptom. Radiologic findings were highly variable. Extrapulmonary and disseminated TB occurred 29.84% and 15.96%, respectively. Multidrug-resistant TB was rare. Treatment using 4 or 5 drugs was commonly associated with hepatotoxicity and graft dysfunction. All-cause mortality was 18.84%. CONCLUSIONS: This large review highlights the complexity of TB after SOT. Reactivation TB, donor-transmitted infection, extrapulmonary involvement, and disseminated disease are common occurrences. Treatment of TB is commonly associated with hepatotoxicity and graft dysfunction.