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Background: Antimicrobial stewardship (AMS) is a coherent set of actions to optimize antimicrobial use, improve patient outcomes, and reduce antimicrobial resistance (AMR). Thailand's national strategic plan has included AMS since 2017. Due to an increased risk of infection and AMR, solid organ transplant (SOT) recipients can benefit from antimicrobial stewardship programs (ASPs). However, the AMS in SOT has not been well defined. Balancing ASPs with the need for early and frequent antimicrobial treatment in this population is challenging. This review assesses the barriers and potential strategies of AMS in SOT in the setting of Thailand., Methods: We used PubMed to identify published articles on AMS in organ transplantation in Thailand from January 2013 to January 2022. We also searched local literature and local data from Google Scholar and Google. Finally, we described the AMS experience at Ramathibodi hospital as a proxy for transplant centers in Thailand., Results: There was no specific article on AMS in SOT in Thailand. At our hospital, ASPs have been part of the hospital's routine patient care, including the practice in the transplant unit. Modifiable challenges to AMS in SOT include prescriber opposition, diagnosis uncertainty, and lack of high quality. Both systems and individualized approaches should be implemented to overcome these barriers. The potential interventions include shortening antibiotic time-out, updating clinical guidelines, continuing education, handshake ASP, adopting new technology, and further research., Conclusions: There are limited data on AMS in organ transplantation in Thailand. Strategic priorities should focus on modifiable barriers tailored to organ transplantation. Quality improvement should be ensured by process and outcome measures., (© 2022 Wiley Periodicals LLC.)

Little is known about immunogenicity after ChAdOx1 nCov-19 vaccination after transplantation. We assessed the vaccine response by antibody testing, surrogate neutralization test (sVNT) against wild-type (WT) and delta variant (DT), and T cell assay in 83 kidney transplant recipients (KTRs) and 52 healthy volunteers (HVs). For KTRs, a positive anti-RBD antibody was seen in 2.8% after one dose and 15.7% after two doses of the vaccine. After two doses, the positivity rate by sVNT was equal (4.9% each, for WT and DT) and was 13.4% by T cell response. Post two doses, KTRs had significantly lower geometric mean titer than HVs (1.93 [95% CI: 1.39-2.69] vs. 248.3 [95% CI: 203.7-302.6] BAU/ml, respectively, p < .001). Daily mycophenolate dose of ≥1000 mg significantly associated with negative seroconversion [risk ratio (RR) of 0.33, 95% CI: 0.15-0.72, p = .005]. Compared with cyclosporine, daily tacrolimus dose of ≤3 mg and >3 mg of tacrolimus significantly associated with negative seroconversion [RR = 0.38 (95% CI, 0.17-0.85, p = .018) and RR = 0.16 (95% CI, 0.37-0.73, p = .018)], respectively. The vaccine was safe and well-tolerated but the immune response after the two doses of ChAdOx1 nCov-19 vaccine in KTRs was very low., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Late-onset cytomegalovirus (CMV) infection (LCI) has been emerging mong solid-organ transplant recipients. We explored clinical characteristics, risk factors, and outcomes of LCI in kidney transplantation (KT) recipients., Methods: A retrospective study of all adult KT recipients with LCIs (that occurred >6 months after transplant) from 2016 to 2018 was conducted. Clinical characteristics and outcomes were extracted. Risk factors of LCI were analyzed using Cox proportional hazards models., Results: A total of 518 KT recipients were included. Ninety-eight percent had donor CMV-seropositive and recipient CMV-seropositive status (D+/R+). Ten (2%) KT recipients developed LCI with a median onset of 14 (interquartile range, 8-15) months. Those included asymptomatic CMV infection (40%) and tissue-invasive disease (60%). CMV D+/R- serostatus and a prior episode of rejection within 6 months were associated with LCI (hazard ratio, 17.35; 95% confidence interval, 3.60-83.63; P < .001) and (hazard ratio, 38.15; 95% confidence interval, 6.15-236.72; P < .001), respectively. There was no difference in the rate of allograft failure and mortality in those with LCI compared with those with early-onset CMV infection., Conclusion: LCI is uncommon after KT. Those with CMV seromismatch and a prior episode of rejection were more likely to develop LCI. Clinical and allograft outcomes were not different among each group., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To investigate clinical and computed tomography (CT) findings of invasive pulmonary aspergillosis (IPA) in patients with systemic lupus erythematosus (SLE) and to explore the relationships of CT findings with clinical characteristics and outcomes., Materials and Methods: Clinical and CT findings of 14 SLE patients with proven (n=4) and probable (n=10) IPA between January 2006 and April 2013 were reviewed retrospectively and related to patients' outcomes., Results: All patients (mean age, 42.3 ± 15.1 years; 11 women, three men) had active SLE, prior corticosteroid, and/or immunosuppressive therapy. Dominant CT findings performed within 10 days of the clinical onset consisted of nodules/masses (100%, 14/14), consolidations (92.9%, 13/14), and ground-glass opacity (85.7%, 12/14). Bilateral, multilobar, and upper-lobe involvement was common. Regardless of dominant patterns, the halo, reversed halo, air-crescent, hypodense, and feeding vessel signs were found in 12 (85.7%), one (7.1%), three (21.3%), seven (50%), and seven (50%) patients, respectively. There was no significant difference in CT findings between the IPA alone (n=5) and co-infection (n=9) groups and between survived (n=4) and non-survived (n=10) patients. The IPA-alone group more frequently had alcohol consumption (p=0.018), haemoptysis (p=0.023), and disseminated aspergillosis (p=0.027) than did the co-infection group. Non-survived patients tended to be older and have a history of recent hospitalisation., Conclusions: IPA is a rare, life-threatening disease affecting SLE patients in the early course of disease with high disease activity requiring corticosteroid and/or immunosuppressive therapy. Dominant CT findings are characteristics of angio-invasive form with a high frequency of the halo sign and bilateral, multilobar, and upper-lobe involvement., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

As the battle against coronavirus disease 2019 pandemic continues, an increase in workload and medical expenses have been a concern to the health care system worldwide. Developing a measure that helps to conserve the health care resource is, therefore, highly desirable, and the pooling of the specimens for testing is one of the attractive strategies. Recently, we showed that saliva could be a potential alternative specimen for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR). In the present study, we performed the pooling of saliva specimens for testing by SARS-CoV-2 RT-PCR. We showed that the saliva pool of either 5 or 10 samples, by allowing the detection of either gene in the pool at an increased cycle threshold cutoff value, further performing individual sample testing in the positive pools did not compromise the detection of SARS-CoV-2., (© 2020 Wiley Periodicals LLC.)

Objectives: Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19., Methods: From 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared., Results: Two-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%-96.6%), and 98.9% (95% CI 96.1%-99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (κ coefficient 0.851, 95% CI 0.723-0.979; p < 0.001)., Conclusions: Saliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance., (© 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Cytomegalovirus (CMV) infection is one of the leading causes of morbidity and mortality in kidney transplantation (KT) recipients. We investigated the association of CMV serostatus and patient outcomes within the first year after KT., Methods: All KT recipients between January 1, 2007 and December 31, 2017 were identified from the Thai Transplant Registry. The prevalence rates of allograft loss and mortality within the first year after KT were estimated by the Kaplan-Meier method. The CMV serostatus in donors (D) and recipients (R) was assessed as a prognostic factor for allograft loss and mortality within the first year by the Cox proportional hazards model., Results: During the 10-year study period (2007-2017), there were 4556 KT recipients with a mean ± standard deviation age of 43 ± 14 years, and 63% of the recipients were male. Deceased-donor KT and induction therapy were performed in 52% and 58% of the recipients, respectively. Among the 3907 evaluable patients, the rates of cases with D + /R + , D + /R - , D - /R + , and D - /R - as the CMV serostatus were 88.9%, 6.1%, 2.9%, and 1.9%, respectively. The estimated prevalence rates of allograft loss and mortality within the first year were 3.8% and 2.8%, respectively. In univariate analysis, CMV D + /R - serostatus was significantly associated with mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.18-3.75; P = .01) but not with an allograft loss (HR, 1.51; 95% CI, 0.85-2.66; P = .16) within the first year after KT. In multivariate analysis, CMV D + /R - serostatus of D + /R - was associated with mortality within the first year after KT (HR, 2.04; 95% CI, 1.05-3.95; P = .04). Other independent prognostic factors for mortality were old recipient age, deceased-donor KT, and hemodialysis after KT., Conclusions: In a national setting with predominant CMV seropositivity in both D and R, CMV seromismatch was associated with poor patient survival within the first year after KT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adjustment of immunosuppression is the main therapy for BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) after kidney transplantation (KT). Studies of BKPyV-specific T cell immune response are scarce. Here, we investigated BKPyV-specific T cell immunity in KT recipients diagnosed with BKPyVAN., Methods: All adult KT recipients with BKPyVAN diagnosed at our institution from January 2017 to April 2018 were included. Laboratory-developed intracellular cytokine assays measuring the percentage of IFN-γ-producing CD4 + and CD8 + T cells, after stimulation with large-T antigen (LT) and viral capsid protein 1 (VP1), were performed both at the time of diagnosis and after adjustment of immunosuppression., Results: We included 12 KT recipients diagnosed with BKPyVAN (7 proven, 4 presumptive, and 1 possible). Those with presumptive BKPyVAN had a median plasma BKPyV DNA load of 5.9 log10 copies/ml (interquartile range [IQR]: 4.9-6.1). Adjusted dosing of mycophenolic acid and tacrolimus with (86%) or without (14%) adjunctive therapies were implemented after diagnosis. There was a significantly higher median percentage of IFN-γ-producing CD4 + T cells to LT at a median of 3 (IQR: 1-4) months after adjustment of immunosuppression compared with at the time of diagnosis (0.004 vs. 0.015; p = 0.047). However, the difference between the median percentage of IFN-γ-producing CD4 + T cells to VP1 and CD8 + T cells to LT and VP1 did not reach statistical significance. Four (33%) patients achieved plasma BKPyV DNA clearance, and the remaining eight (67%) patients had persistent BKPyV DNAemia. Although eight (67%) patients developed allograft dysfunction, none required hemodialysis., Conclusions: We observed a marginal trend of BKPyV-specific CD4 + T cell recovery after adjustment of immunosuppression in KT recipients diagnosed with BKPyVAN. A further study would be benefited to confirm and better assess BKPyV-specific immune response after KT.

Objective: Adenovirus (ADV) infection after kidney transplantation (KT) causes significant morbidity. Patient characteristics and outcomes of ADV infection in KT recipients were investigated., Method: All adult KT recipients with ADV infection between January 2015 and June 2019 were included. ADV infection/disease was defined as detection of ADV DNA in clinical specimens/plus symptoms. Clinical and laboratory findings, treatments, and outcomes were assessed., Results: Adenovirus infection was diagnosed in 24 of 751 (3.2%) KT recipients. Twenty (83%) were male with a median age of 47 years (interquartile range [IQR], 36-58). Fifteen (63%) underwent deceased donor KT, and 13 (54%) received induction therapy. Twenty-one (88%) and 4 (17%) patients developed hemorrhagic cystitis and disseminated disease, respectively. There were equal distributions of early-onset (EOI) (≤3 months) and late-onset (LOI) (>3 months) infections. Patients who were diagnosed with EOI had lower median absolute lymphocyte counts compared with those with LOI (735/mm 3 [IQR, 543-1123] vs 1122/mm 3 [IQR, 784-1344], P = .04). All achieved resolution after reduction of their immunosuppression regimen and 13 (54%) received cidofovir therapy. Eighteen (75%) developed allograft dysfunction, of which 67% were transient. One (4%) underwent nephrectomy for allograft failure and 1 (4%) died (non-ADV-related). Patients with EOI were more likely to receive cidofovir therapy (75% vs 33%, P = .04) and develop other opportunistic infections (75% vs 8%, P < .001)., Conclusions: Adenovirus infection after KT typically involves a genitourinary system and transiently impairs an allograft function. Those who developed early infection tend to have more lymphopenia, coinfection, and receive antiviral therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Human adenovirus (HAdV) infection can cause substantial morbidity in kidney transplant (KT) recipients. Cell-mediated immunity plays an important role in controlling HAdV infection after KT., Methods: We prospectively (January 2015 to June 2018) investigated the absolute lymphocyte count (ALC) and interferon-γ-producing CD4 + and CD8 + T cells at diagnosis and at viral clearance by an intracellular cytokine assay after stimulating with HAdV whole lysate, hexon, and penton proteins. HAdV infection was defined as the presence of HAdV DNA load in plasma or clinical specimens measured by the polymerase chain reaction assay., Results: Eighteen adult KT recipients were diagnosed with HAdV infection at a median of 16 months (interquartile range [IQR], 2-39) after KT. The majority (94%) had HAdV-associated hemorrhagic cystitis. The median ALC at viral clearance was significantly higher compared with diagnosis (2257 cells/mm 3 [IQR, 1544-3078] vs 1001 cells/mm 3 [IQR, 641-1385]; P < 0.001). Eleven patients underwent measurement of the HAdV-specific T-cell response. The median numbers of CD4 + and CD8 + T cells at viral clearance were significantly higher compared with diagnosis (448 cells/mm 3 [IQR, 248-651] vs 215 cells/mm 3 [IQR, 159-272], P = 0.02; and 623 cells/mm 3 [IQR, 242-772] vs 235 cells/mm 3 [IQR, 129-266], P < 0.01), respectively. The median percentages of penton-specific CD4 + and hexon-specific CD8 + T cells at viral clearance were significantly higher compared with diagnosis (0.012% vs 0%, P = 0.03%; and 0.136% vs 0.016%, P = 0.003, respectively)., Conclusions: Our findings suggest a trend of ALC and HAdV-specific T-cell immune restoration in KT recipients who achieve successful HAdV clearance., (© 2019 Wiley Periodicals, Inc.)

Background: Current guidelines recommend echinocandins as first-line therapy for candidemia. However, several non-Candida yeast are non-susceptible to echinocandins (echinocandin non-susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1-year, laboratory surveillance programme in Asia., Methods: Non-duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient., Results: Of 2155 yeast isolates evaluated, 175 (8.1%) were non-Candida yeast. The majority of non-Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non-tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology-oncology units (2.9%). Cryptococcus accounted for the majority of the non-Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%)., Conclusions: Isolation of non-Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries., (© 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.)

Background: Kidney transplant (KT) recipients in dengue-endemic areas are at risk of exposure. We investigated the epidemiology and outcomes from dengue in KT recipients at our transplant center and conducted a literature review., Materials and Methods: We conducted a 20-year retrospective study of KT recipients who were diagnosed with laboratory-confirmed dengue from January 1997 to September 2017 according to the 2009 World Health Organization (WHO) classification. We analyzed clinical characteristics and treatment outcomes., Results: There were 13 (0.7%) dengue cases among 1917 KT recipients with a median age of 39 years (interquartile ranges [IQR], 22-46); 54% were males. Cases occurred with a median onset of 24 months (IQR, 6-122) after KT. Dengue was diagnosed via dengue NS1 antigen (85%), IgM antibodies (38.5%), or RT-PCR (15.4%). Patients were classified as having dengue without warning sign (30.8%), with warning sign (53.8%), or severe dengue (15.4%). All patients resolved without complications, except one had hemophagocytic lymphohistiocytosis. Ten (76.9%) patients experienced eGFR reduction with a median of 13.7 mL/min/1.73 m 2 (IQR, 8.3-20.5); eight (80%) had a full allograft function recovery., Conclusions: Dengue in KT recipients in endemic areas is uncommon. Although a transient decline in allograft function can occur, the overall clinical and allograft outcomes seem to be favorable., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cytomegalovirus (CMV) is an important cause of infectious complications after kidney transplantation (KT), especially among patients receiving antithymocyte globulin (ATG). CMV infection can result in organ dysfunction and indirect effects such as graft rejection, graft failure, and opportunistic infections . Prevention of CMV reactivation includes pre-emptive or prophylactic approaches. Access to valganciclovir prophylaxis is limited by high cost. Our objective is to determine the burden and cost of treatment for CMV reactivation/disease among KT recipients who received ATG in Thailand since its first use in our center. Methods: We conducted a single-center retrospective cohort study of KT patients who received ATG during 2010-2013. We reviewed patients' characteristics, type of CMV prophylaxis, incidence of CMV reactivation, and outcome (co-infections, graft function and death). We compared the treatment cost between patients with and without CMV reactivation. Results: Thirty patients included in the study had CMV serostatus D+/R+. Twenty-nine patients received intravenous ganciclovir early after KT as inpatients. Only three received outpatient valganciclovir prophylaxis. Incidence of CMV reactivation was 43%, with a median onset of 91 (range 23-1007) days after KT. Three patients had CMV end-organ disease; enterocolitis or retinitis. Infectious complication rate among ATG-treated KT patients was up to 83%, with a trend toward a higher rate among those with CMV reactivation ( P = 0.087). Patients with CMV reactivation/disease required longer duration of hospitalization ( P = 0.018). The rate of graft loss was 17%. The survival rate was 97%. The cost of treatment among patients with CMV reactivation was significantly higher for both inpatient setting ( P = 0.021) and total cost ( P = 0.035) than in those without CMV reactivation. Conclusions: Burden of infectious complications among ATG-treated KT patients was high. CMV reactivation is common and associated with longer duration of hospitalization and higher cost., Competing Interests: No competing interests were disclosed.

Background: Data on drug-resistant cytomegalovirus (CMV) infection in solid organ transplantation (SOT) are not often reported from resource-limited settings. We aimed to investigate the epidemiology and outcomes of this infection in SOT recipients at our institution., Methods: This was a retrospective study conducted from January 2012 to May 2015. We included all SOT recipients who were suspected for drug-resistant CMV infection. Genotypic assay for UL97 gene mutation was analyzed by real-time polymerase chain reaction. Patients were reviewed for demographic data, clinical presentation, virologic data, treatment, and outcomes., Results: The population consisted of 18 (12 kidney, 6 liver) SOT recipients with a median age of 20 years (interquartile range [IQR], 1-49); 44% were male. Anti-CMV resistance testing was analyzed at a median time of 23 days (IQR, 14-33) after initiation of anti-CMV therapy with a median CMV load of log 3.79 copies/mL (IQR, 3.37-4.58). During a median period of 2 years (IQR, 1-3), 6 SOT recipients were identified with UL97 gene mutation in codon 460, conferring ganciclovir (GCV) resistance. Patients with UL97 gene mutation had a longer mean duration of CMV DNAemia compared with those without mutation (263 vs 107 days; P = .04). All patients received high-dose GCV. Two patients received foscarnet and cidofovir. Two patients died (non-CMV-related), and 4 patients developed opportunistic infections other than CMV., Conclusions: GCV-resistant CMV infection in SOT recipients is an emerging clinical problem in resource-limited country. Those with UL97 mutation CMV infection have prolonged duration of CMV DNAemia. Clinicians should be aware of this condition when caring for SOT recipients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the association of genetic variants of CYP2C19 (CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles) and voriconazole trough plasma concentrations in Thai patients with invasive fungal infection. A total of 285 samples from patients with invasive fungal infection and treated with voriconazole were prospectively enrolled. At steady state, trough voriconazole concentrations were measured using tandem mass spectrophotometry and high performance liquid chromatography. The genetic variants in the CYP2C19 gene were genotyped for CYP2C19*2 (G681A), CYP2C19*3 (G636A) and CYP2C19*17 (C-806T) on plasma voriconazole level. Voriconazole Ctrough levels were positively associated with CYP2C19*3. The median Ctrough level for patients with the 636GA genotype (2.109, IQR 1.054-4.166 μg/ml) was statistically significantly higher than those with the 636GG genotype (1.596, IQR 0.755-2.980 μg/ml), P = 0.046. The patients with a poor metabolizer (PM; CYP2C19*2/*2, *2/*3) had voriconazole Ctrough level of 1.900 (IQR, 1.130-3.673 μg/ml). This was statistically significantly higher than that seen with the extensive metabolizer phenotype (1.470; IQR, 0.632-2.720 μg/ml), P = 0.039. An association between CYP2C19 variant alleles and high voriconazole plasma level was identified. Therefore, determining the CYP2C19 genotype before initiation of voriconazole treatment may be useful in optimizing the dosing regimen in Thai patients with invasive fungal infections., (Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Objective: Varicella zoster (VZV) is a potentially life-threatening infection after kidney transplantation (KT) but data on the incidence and outcome of late KT VZV infection is limited., Material and Method: A retrospective study of disseminated VZV infection (D-VZV) in post KT patients was conducted between 2003 and 2013. Acyclovir prophylaxis was given routinely for six months after KT Statistical analyses were performed by SPSS software version 17.0., Results: Prevalence of D-VZV was 2% [22/1,032 patients]. Patients median age were 40 (21-67) years old and 12 (55%) were male. Timing of the infection was mostly (68.2%) late (> 1 year) post KT The majority of maintenance immunosuppressive drug included prednisolone (95.5%), cyclosporine (77.3%), mycophenolate (68.2%). Two (9.1%) had a recent VZV exposure and four (18%) received intensified immunosuppression before the diagnosis. Common clinical presentations were lymphopenia (54.5%), generalized vesicular rash (50%), and multi-dermatomal distribution (50%) while liver involvement was infrequent (9.1%). None had pneumonitis or neurological involvement. All cases received systemic acyclovir with the median duration of 14 (3-31) days. One had received IVIG for fulminant hepatitis. Immunosuppressive drug/s was reduced in 59%. Median duration of hospitalization was seven (3-37) days. None of patients died. The median follow-up duration was 1939 (IQR 804-2440) days. Recurrent infection was uncommon (4.5%). Secondary prophylaxis was given only in one patient with fulminant VZV hepatitis., Conclusion: Incidence of D-VZV post KT was low. Treatments with intravenous acyclovir and reduction of immunosuppression without the use of VZV IgG provided favorable outcome in resource-limited settings.

The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16-4.53 per 1000 discharges) and countries (range 0.25-2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Data on the immunogenicity (IG) of the influenza vaccine among patients at high risk of influenza-related complication are limited., Methods: We studied the antibody titer following a single dose of monovalent 2009 influenza A (H1N1) vaccine between groups of adult patients who were healthy, those with chronic renal failure (CRF), kidney transplant (KT) recipients, and human immunodeficiency virus (HIV)-infected patients. The IG (primary endpoints) was accessed at 4 weeks after vaccination. The secondary endpoint was safety of the vaccine., Results: A total of 293 patients were studied. Patients' mean age was 41(standard deviation [SD], 13.3) years old. At baseline, mean age (P < .001), history of vaccination in a prior year (P < .001), and geometric mean titers (GMT; P < .001) significantly differed between each groups and the majority (70%) of participants had the hemagglutination inhibition titer <1:10. The IG of the vaccine was highest in the healthy group (71.4 %). The response rate among CRF, KT, and HIV groups was 42.4% (risk ratios [RR], 0.72; 95% confidence interval [CI], 0.5-1.02), 31.9% (RR, 0.51; 95% CI, 0.34-0.76), and 29.7% (RR, 0.42; 95% CI, 0.3-0.6), respectively. The vaccine was well-tolerated in all studied groups. Thirty (10.2%) patients experienced at least 1 adverse reaction but systemic reaction was uncommon (3.4%)., Conclusions: A single dose of monovalent 2009 influenza A (H1N1) vaccine result in poor IG among high-risk populations, including CRF, KT and HIV patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We aimed to investigate clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment., Materials and Methods: We retrospectively reviewed the medical records, initial and follow-up chest computed tomography scans and/or radiographs for initial clinical and radiologic manifestations and outcomes following antifungal treatment of 12 immunocompetent patients diagnosed with pulmonary cryptococcosis between 1990 and 2012., Results: Twelve patients (age range, 21-62 years; males, eight patients [66.7%]) were included. Nine (75%) patients were symptomatic, eight of whom had disseminated infection with central nervous system involvement. Initial pulmonary abnormalities consisted of single nodules/masses (n=5), single segmental or lobar mass-like consolidation (n=3), multiple cavitary and noncavitary nodules (n=1), and multifocal consolidation plus nodules (n=3). These lesions ranged from less than 1 cm to 15 cm in greatest diameter. Distinct subpleural and lower lung predominance was observed. Seven patients (58.3%) had one or more atypical/aggressive findings, namely endobronchial obstruction (n=4), calcified (n=1) or enlarged (n=4) mediastinal/hilar lymph nodes, vascular compression (n=1), pericardial involvement (n=1), and pleural involvement (n=2). Following antifungal therapy, radiologic resolution was variable within the first six months of eight nonsurgical cases. Substantial (>75%) improvement with some residual abnormalities, bronchiectasis, cavitation, and/or fibrotic changes were frequently observed after 12-24 months of treatment (n=6)., Conclusion: Pulmonary cryptococcosis in immunocompetent patients frequently causes disseminated infection with atypical/aggressive radiologic findings that are gradually and/or incompletely resolved after treatment. The presence of nonenhanced low-attenuation areas within subpleural consolidation or mass and the absence of tree-in-bud appearance should raise concern for pulmonary cryptococcosis, particularly in patients presenting with meningitis.

Appendicitis is a condition characterized by inflammation of the vermiform appendix, which is commonly caused by bacterial infections and rarely caused by fungal organisms. In the present study, we reviewed the prevalence, clinicopathological features, and therapeutic management of fungal appendicitis. During July 2010 to June 2011, the pathology of 262 resected vermiform appendices was reviewed. Fungal appendicitis occurred in 1.15%, including two cases of Candida spp and one case of Aspergillus spp infection. All patients were immunocompromised and presented with the classical signs and symptoms of appendicitis with the onset of illness less than two days. They were considered for acute appendicitis and underwent appendectomy. The histopathology of the resected vermiform appendix showed fungal organisms with suppurative inflammation and secondary periappendiceal peritonitis. The curative treatment was presented in 1-out-of-3 cases. One patient was alive during a follow-up of eight months. Two patients died, and an autopsy was performed in one case. Although fungal appendicitis was uncommon, the disease might occur among immunosuppressed patients who have developed classical signs and symptoms of appendicitis. Early diagnosis and prompt surgery with medical treatment are associated with a survival advantage.

Cerebral mycosis is a significant cause of morbidity among immunocompromised populations. We present here a case of cerebral infection with Scedosporium apiospermum and Phaeoacremonium parasiticum in a 49-year-old renal transplant recipient. Fourteen years after renal transplantation, the patient presented with invasive pulmonary aspergillosis treated with intravenous liposomal amphotericin B. The patient had clinical and radiographic improvement. However, 6 weeks later, the patient presented with cerebral infection. Magnetic resonance imaging revealed multiple rim enhancing brain abscesses. Brain and cerebrospinal fluid cultures ultimately grew Scedosporium apiospermum and Phaeoacremonium parasiticum. The patient was treated with voriconazole for 6 months and had clinical and radiologic improvement. We believe this is the first reported case of co-infection of the brain with scedosporiosis and phaeohyphomycosis in a renal transplant recipient, who had received intravenous liposomal amphotericin B. Voriconazole may represent a new therapeutic option for these simultaneous infections in the brain.

Background: Tuberculous lymphadenitis (TBL) is the most common form of extrapulmonary tuberculosis. Currently, the standard diagnostic test for TBL is culture, which takes more than several weeks to yield results. We studied a real-time polymerase chain reaction (PCR) for rapid detection of Mycobacterium tuberculosis in cervical lymph node specimens obtained from patients in a country where the tuberculosis incidence is high., Methods: Patients with cervical lymphadenopathy were prospectively enrolled between April 2009 and March 2010. Clinical specimens obtained through fine-needle aspiration (FNA) and excisional biopsy were tested for M. tuberculosis by the COBAS TaqMan MTB Test, a real-time PCR assay for detecting the 16S ribosomal RNA gene of M. tuberculosis. Mycobacterial culture and histopathological findings from tissue biopsy specimens were used as a reference standard for sensitivity and specificity calculations., Results: Of 73 patients, 41 received a diagnosis of TBL. For biopsy specimens, the sensitivity of real-time PCR was 63.4%, and the specificity was 96.9%. For FNA specimens, the sensitivity was 17.1%, and the specificity was 100%. The sensitivity of real-time PCR of biopsy specimens was comparable to that of tissue culture but significant lower than that of histopathological examination (P < .01)., Conclusions: Real-time PCR did not increase the yield for rapid diagnosis of TBL.

Background: While prevention of cytomegalovirus (CMV) infection after kidney transplantation (KT) has become a standard practice in Western countries, this approach is not always feasible in Thailand. In order to argue for the need for CMV prevention, the knowledge on the incidence and impact of the CMV infection following KT is highly desirable., Methods: We retrospectively reviewed medical records of adult patients who underwent KT at our transplant center between January 2006 and December 2010. Patients who developed CMV viremia within 1 year after transplantation were studied for the incidence, risk factors, and outcome of symptomatic infection. The threshold value of blood CMV DNA load indicating symptomatic infection was also analyzed., Results: Symptomatic CMV infection occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3-30) weeks after KT. At initial presentation, coexisting opportunistic infection was common (44%) and gastrointestinal tract was the major type of organ involvement (44%). Between groups of patients with symptomatic and asymptomatic CMV infection, the mean (± standard deviation) level of blood viral load were significantly higher in the first group [4.2 (± 0.5) vs 3.3 (± 0.4) log copies/mL]. From multivariate analysis, associated factors of symptomatic infection included acute rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44, P = .019). Death (13%) and graft failure (13%) were significantly higher among the symptomatic infection group than those in the no-infection group (P = .005 and .03, respectively)., Conclusion: Despite a low incidence rate, symptomatic CMV infection clearly resulted in significant morbidity following KT. In Thailand, the prevention of CMV infection should be prioritized among high-risk KT populations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In 2009, a novel influenza A (H1N1) virus emerged and rapidly spread around the world, leading to a pandemic. In contrast to the high rate of primary infection, reinfection with influenza A (H1N1) 2009 is rather rare. In this report, we describe a case of influenza A (H1N1) 2009 reinfection that occurred within an interval of 5 months in Thailand., (Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

We aimed to report the coverage and safety of the influenza A (H1N1) 2009 monovalent vaccination (Panenza; Sanofi Pasteur, Val de Reuil Cedex, France) among health care personnel (HCP) in a university hospital setting in Thailand. The hospital set up a system to vaccinate HCP and did surveillance of the adverse effects (AEs). During a 4-week period, 6,210 (78.7%) HCP were vaccinated. There were 82 reported nonserious AEs among 32 HCP. The most common AE was fatigue/uncomfortable feeling (24%)., (Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis. Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were "histoplasmosis" and "adrenal gland". Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome. The onset of symptoms ranged from one to three months. Addison's disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter. The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years.

Information on the clinical spectrum and management of adenovirus infection after kidney transplantation is limited. From April 2007 to April 2010, 17 kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2-300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6-month follow-up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Data on the epidemiology and route of acquisition of adenovirus (ADV) infection after kidney transplantation are limited. From April 2007 to March 2010, there were 17 cases of ADV infection: namely, 2 from April to December 2007; 8 from January to December 2008; 4 from January to December 2009; and 3 from January to March 2010. Most cases occurred in October and November (n = 8; 47.1%), followed by February to April (n = 6; 35.3%) and July (n = 3; 17.6%)., Methods: From April 2007 to August 2009, the diagnosis of ADV infection was made based on patient symptoms. From September 2009 to March 2010, in addition to symptoms, the diagnosis was complemented by urine surveillance for ADV using real-time polymerase chain reaction (PCR) prospectively performed every 1-2 weeks among recipients of living-related kidney, starting at week 2 posttransplantation for a total of 8-12 weeks. Before transplantation, recipients and donors were screened for ADV in urine and also using nasal swab., Results: Only 1 of the 24 patients displayed a positive ADV PCR in the urine surveillance study. A local investigation during a cluster of cases in October 2008 showed 2 patients who developed ADV after sharing a room in the transplant unit. Although nosocomial transmission was probable, the majority of cases were scattered over time rather than clustering in 1 time period., Conclusion: These findings suggested that ADV infection cases occurred after exogenous exposure. In a resource-limited country, early diagnosis of ADV is justified for patients with compatible symptoms complemented by intense infection control to prevent nosocomial transmission from a confirmed case., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Determine and compare the clinicopathological findings of cerebral aspergillosis with cerebral candidiasis., Material and Method: The medical records with cerebral aspergillosis and cerebral candidiasis in Ramathibodi Hospital between January 1997 and December 2008 were analyzed. The criterion for the diagnosis of cerebral aspergillosis and cerebral candidiasis was the evidence of fungal elements from histopathologic section. The age, gender neurological manifestations, duration of symptom, associated underlying disease, predisposing risk factor, laboratory data, extent of systemic organ involvement and treatment outcome were analyzed., Results: The present study included cerebral aspergillosis (n = 41) and candidiasis (n = 15). There were 23 male and 33 female patients. The mean and median ages at diagnosis were 39.7 and 45 years, respectively (range, 1 month to 87 years). The clinical presentations included alteration of consciousness (69.6%), fever (60.7%), weakness of the extremity (14.3%), cranial nerve palsy (12.5%), headache (12.59%) and seizure (5.4%). One third of the cases had underlying hematologic malignancy. The cerebral aspergillosis and cerebral candidiasis were associated with corticosteroids treatment in 32.1%. The frequent associated sites of fungal infection included the lungs (73.2%), alimentary tract (33.9%) and sinonasal tract (19.6%)., Conclusion: A diagnosis of cerebral aspergillosis and cerebral candidiasis requires a high index of suspicion especially in immunocompromised patients who presented with alteration of consciousness, fever, focal neurological deficit, headache, and seizure. The patients with cerebral aspergillosis and cerebral candidiasis manifest with similar clinicopathologic features. However, the sinonasal tract infection and abscess formation are more common in cerebral aspergillosis. Associated alimentary tract infection is commonly seen in cerebral candidiasis.

ADV and PMV infection have increasingly been documented as significant complications following allo-HSCT. Despite increasing recognition, characteristics and outcome of CMV, ADV, and PMV viral co-infection remain obscured. In this study, a retrospective quantitative PCR analysis of ADV, PMV (BKV and JCV) was performed from pediatric patients' stored blood samples previously tested for CMV viremia after allo-HSCT. Clinical and virological characteristics and outcome among patients with and without viral co-infection were analyzed and compared. From 2001 to 2006, 219 blood samples from 69 patients were studied. Viral DNA was present in 119 samples (52.9%).The proportion of viremia was highest for BKV (30.6%), followed by CMV (20.9%), ADV (9.1%), and JCV (0.5%). Viral co-infection occurred in 17 patients (24.6%), with CMV/BKV as the most common type (11.6%), followed by CMV/ADV (4.3%) and ADV/BKV (2.9%). From multivariate analysis, factors associated with viral co-infection were acute GVHD (OR 4.57; 95% CI 1.9-10.96, p = 0.001), level of blood CMV viral load (OR 1.53; 95% CI 1.24-1.89, p < 0.001), and level of blood ADV viral load (OR 1.56; 95% CI 1.05-2.32, p = 0.027). Higher probability of developing viral disease was strongly associated with more types of virus detected in blood (p < 0.001). Significant difference in the causes of death was observed among patients with and without viral co-infection (p = 0.014). Infection (87.5%) was the major cause of death of patients with viral co-infection, whereas relapse of hematologic disease (70%) was the major cause of death of patients with mono-viral infection. Viral co-infection is a common and significant infectious complication in pediatric recipients of allo-HSCT. Blood monitoring of CMV, ADV, and BKV is suggested among pediatric patients who develop GvHD or who have rising of CMV or ADV viremia following allo-HSCT.

We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients.

Invasive candidiasis has emerged as an important nosocomial infection, especially in critically ill patients. The incidence of candidaemia in Intensive Care Units (ICUs) is 5- to 10-fold higher than in the entire hospital and the crude mortality rate of patients with candidaemia is between 35% and 60%. Candida albicans remains the predominant cause of invasive candidiasis in ICUs, followed by Candida tropicalis, Candida glabrata and Candida parapsilosis. Invasive isolates of Candida spp. remain highly susceptible to fluconazole (>90% susceptible), although among Asia-Pacific countries the susceptibility rate of C. glabrata to fluconazole varies widely from 22% to 72%. Early diagnosis and prompt initiation of antifungal therapy are crucial for the effective treatment of invasive candidiasis. However, invasive candidiasis is difficult to diagnose owing to its non-specific clinical features, and delayed therapy is a major contributor to poor outcomes. Combining clinical risk factors with Candida colonisation parameters appears promising for guiding early interventions. Because of considerable regional variability, local epidemiological knowledge is critical in the effective management of invasive candidiasis among ICU patients in Asia-Pacific.