Epidemiology and Factors Associated with Treatment Success of Invasive Fungal Infections Among Newly Hematologic Malignancy Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant in Thailand.

Purpose: Invasive fungal infection (IFI) causes disability/death in patients with hematologic malignancy (HM) receiving chemotherapy or hematopoietic stem cell transplant (HSCT). There is limited epidemiological data, treatment outcomes, and factors associated with IFI treatment success in Thailand. This study aimed to identify factors associated with IFI treatment success among new HM patients receiving chemotherapy or HSCT, determine IFI incidence among HM patients receiving chemotherapy or HSCT, and the IFI incidence of a breakthrough in patients receiving primary antifungal prophylaxis, and identify antifungal drugs susceptibility. Patients and Methods: This study reviewed the charts of patients aged ≥ 15 years with newly HM who received chemotherapy or HSCT between January 2016 and June 2021 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The 2020 EORTC/MSG criteria were used to diagnose IFI. IFI treatment success factors were evaluated using logistic regression. Results: Ninety-two patients with 107 episodes of IFI met the inclusion criteria. IFI incidence on proven and probable cases among newly HM patients receiving chemotherapy or HSCT was 7%. Most infections (38.3%) occurred during the induction-phase chemotherapy. Aspergillosis (35.5%) was the commonest IFI, followed by candidiasis (11.2%), Pneumocystis jirovecii pneumonia (8.4%), mucormycosis (3.7%), and others, respectively. The 12-week IFI treatment success rate was 67.3%. It was associated with age < 60 years, absence of coinfection, and the receipt of appropriate empirical therapy on the first day of IFI diagnosis. The incidence of breakthrough IFI from proven and probable cases in patients receiving primary antifungal prophylaxis was 6.1%. Most fungal pathogen isolates were still highly susceptible to antifungal drugs. Conclusion: The IFI treatment success in patients with HM or HSCT in our study was high. Close monitoring of coinfected patients aged ≥ 60 is recommended. Appropriate antifungal drugs are essential for clinical outcomes.

Bacterial Urinary Tract Infection and Early Asymptomatic Bacteriuria in Kidney Transplantation Still Negatively Affect Kidney Transplant Outcomes in the Era of Modern Immunosuppression and Cotrimoxazole Prophylaxis.

Risk factors and consequences of urinary tract infection (UTI) post-kidney transplant have been variously reported by studies that were heterogenous in immunosuppressants and prophylactic protocols. We aimed to clarify the risks and consequences of UTI in kidney transplant recipients with post-transplantation cotrimoxazole prophylaxis in the context of modern immunosuppression. This retrospective cohort included kidney transplant recipients receiving tacrolimus, mycophenolate, prednisolone, and cotrimoxazole for bacterial UTI prophylaxis. Recipients were categorized into non-UTI and UTI groups. Asymptomatic bacteriuria (ASB) was screened in the first 3 months and was evaluated for association with UTI. Of 348 kidney transplant recipients, 129 were in the UTI group and 219 in the non-UTI group. UTI risk factors were female sex, body mass index ≥ 25 kg/m2, human leukocyte antigen mismatch, and panel reactive antibody ≥ 50%. Recipients with recurrent UTI had inferior allograft function compared with non-UTI recipients. Patient survival was significantly lower in recipients with UTI in the first post-transplant month. Higher degree of immunosuppressions was associated with recurrent UTI and drug-resistant organisms. In conclusion, UTI continues to negatively affect graft function and survival of kidney transplant recipients. Treating ASB in the first 3 months did not reduce the UTI incidence in the first transplantation year.

The first report of kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and literature review: Encouragement for developing countries in Southeast Asia.

Patients with human immunodeficiency virus infection are at risk of chronic kidney disease and end-stage renal disease. Human immunodeficiency virus infection impedes patients' accessibility to transplantation in Thailand and other developing countries in Southeast Asia, where the burdens of human immunodeficiency virus infection and chronic kidney disease are rapidly increasing. We report the successful kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and provide brief information about the current knowledge of human immunodeficiency virus medicine and transplantation that are needed for conducting kidney transplantations in such patients. Patient selection and evaluation, the choice of antiretroviral therapy, immunosuppressive regimens, and infectious complications are reviewed and discussed. The aim is to encourage kidney transplantation in end-stage renal disease patients with well-controlled human immunodeficiency virus infection, especially in countries where the prevalence of human immunodeficiency virus infection is high and the accessibility to transplantation is still limited.

A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country.

BACKGROUND: Tuberculosis (TB) is considered as a challenge issue in solid organ transplant recipients because of high morbidity and mortality. Active TB after transplant mostly occurs from reactivation of latent infection. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population, however data from high endemic area is scarce. METHODS: A matched single-center, case-control study was conducted in our institute. Cases were defined as newly diagnosed confirmed or clinical active TB in patients who underwent kidney transplant (KT) between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. RESULTS: Between study period, KT was performed in 787 patients. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 confirmed and 7 clinical diagnosed cases. The global incidence of TB in our population was 315 cases per 100 000 patients per year. Among 27 cases, pulmonary involvement was the most common (48.1%) followed by disseminated (18.5%), extrapulmonary (14.8%), pleura (11.1%) and pleuropulmonary (7.4%) TB. Allograft rejection was significantly associated with active TB (P < .001). The median onset duration of infection was 17 months (IQR, 4-59 months) after KT. Twenty-four (88.9%) patients received rifampicin containing regimen for treatment with median duration of 10 months (IQR, 6-12 months). All patients were cured after complete treatment, however those with TB remained having unfavorable outcomes including higher all-cause mortality and graft loss. CONCLUSIONS: Incidence rate of TB in KT recipients is higher than normal population. Allograft rejection was identified as a significant risk factor. Increase unfavorable outcomes including graft loss and mortality were also observed among patients with TB.

A case of successful treatment of severe COVID-19 pneumonia with favipiravir and tocilizumab in post-kidney transplant recipient.

We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.

Post-transplant Lymphoproliferative Disorder of Naso-orbital Region in Adult Renal Transplant Recipients: A Case Report and Literature Review.

Post-transplant lymphoproliferative disorder (PTLD) is an uncommon but fatal complication following both solid organ and hematologic stem cell transplantations. Epstein-Barr virus (EBV) has been considered a main etiologic agent causing PTLD, especially in the first year after transplantation. Extranodal manifestations are frequently found in PTLD; however, naso-orbital involvement in adults is rare. We report a case of EBV-associated PTLD of the naso-orbital region in a 72-year-old patient that occurred 10 years after kidney transplant. Six additional adults with naso-orbital PTLD were identified after completing this literature review, including 2 cases with eyelid swelling, 3 cases with proptosis, and 1 case with facial numbness. The majority of cases occurred after 1 year of transplantation and were associated with EBV. This report emphasizes recognizing PTLD as differential diagnosis in transplant recipients who present with naso-orbital symptoms.

Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective
.

BACKGROUND: Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS: Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS: A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION: Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

Skin Manifestations in Patients with Adult-onset Immunodeficiency due to Anti-interferon-gamma Autoantibody: A Relationship with Systemic Infections.

Adult-onset immunodeficiency due to anti-interferon-γ autoantibody is an emerging acquired immunodeficiency with frequent skin manifestations. A retrospective chart review was conducted and identified 41 patients with the syndrome. Skin involvement was detected in 33 (80%) patients, 15 (45%) with infective skin diseases and 27 (82%) with reactive skin disorders. Reactive lesions were mostly neutrophilic dermatoses, e.g. Sweet syndrome. Of note, the presence of neutrophilic dermatoses was highly associated with infections of other sites. An adjusted odds ratio for the existence of infections in patients with neutrophilic dermatoses was 14.79 (95% CI: 5.13, 42.70; p < 0.001). Moreover, neutrophilic dermatoses were significantly correlated with opportunistic infections observed in those with defects in cell-mediated immunity including non-tuberculous mycobacterium and disseminated fungal infection. The odds ratio for opportunistic infections in the presence of neutrophilic dermatoses was 12.35 (95% CI: 5.00, 30.55; p <0.001). Thus, the presence of neutrophilic dermatoses in patients with the syndrome can signal opportunistic infections that warrant physician attention.

Common viral infections in kidney transplant recipients.

Infectious complications have been considered as a major cause of morbidity and mortality after kidney transplantation, especially in the Asian population. Therefore, prevention, early detection, and prompt treatment of such infections are crucial in kidney transplant recipients. Among all infectious complications, viruses are considered to be the most common agents because of their abundance, infectivity, and latency ability. Herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, hepatitis B virus, BK polyomavirus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide because of their wide range of distribution. As DNA viruses, they are able to reactivate after affected patients receive immunosuppressive agents. These DNA viruses can cause systemic diseases or allograft dysfunction, especially in the first six months after transplantation. Pretransplant evaluation and immunization as well as appropriate prophylaxis and preemptive approaches after transplant have been established in the guidelines and are used effectively to reduce the incidence of these viral infections. This review will describe the etiology, diagnosis, prevention, and treatment of viral infections that commonly affect kidney transplant recipients.

Comparison of Preemptive Therapy and Antiviral Prophylaxis for Prevention of Cytomegalovirus in Seropositive Liver Transplant Recipients.

BACKGROUND: Few studies have directly compared preemptive therapy (PET) and antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in CMV seropositive (R+) orthotopic liver transplant (OLT) recipients. METHODS: We prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive negative weekly PCR results) and compared them with a historical cohort of 156 R+ recipients who received AP (valganciclovir, 900 mg daily for 3 months). RESULTS: Patient characteristics were similar between PET and AP cohorts (P > 0.05 all comparisons). In the PET group, 24% (39/160) developed CMV viremia greater than 250 IU/mL at a median of 42 (range, 7-93) days post-OLT. CMV monitoring adherence in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV disease, acute allograft rejection, major infection, or death in the PET and AP cohorts was not significantly different: 2% versus 2%, 19% versus 16%, 10.5% versus 10.8%, and 5% versus 8%, respectively (P > 0.05 all comparisons). The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP: 24% versus 100%, P < 0.001, and 15.8 versus 81 g per patient, P < 0.001, respectively. CONCLUSIONS: PET is feasible in a nonresearch setting and is associated with similar CMV disease rates and other clinically relevant outcomes to AP in CMV seropositive liver transplant recipients.

B-cell activating factor, a predictor of antibody mediated rejection in kidney transplantation recipients.

AIM: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection. Recipients were stratified by pre-transplant DSA and BAFF at day 7 into four groups. RESULTS: During the study period, 13.2% of the recipients demonstrated subclinical-ABMR at 6 months, without patient with clinical ABMR presentations. Overall mean BAFF at day 7 was 393 pg/mL (95% CI = 316-471 pg/mL). The optimal cut-off value for low vs. high BAFF level was 573 pg/mL, with sensitivity and specificity at 77.8% and 88.1%, respectively. Fifty percent of recipients with high BAFF at day 7 (14 patients) and only 3.7% of patients with low BAFF demonstrated ABMR (P < 0.05). Indeed, ABMR was more common in patients high BAFF level (hazard ratio = 7.30; 95% CI = 3.77-14.15). The prevalence of ABMR among negative pre-transplant DSA/low BAFF, positive DSA/low BAFF, negative DSA/high BAFF, and positive DSA/ high BAFF recipients were 4.4, 0, 37.5 and 66.7%, respectively (P < 0.05). CONCLUSIONS: Post-transplant ABMR can be predicted by perioperative serum BAFF level. Together with DSA testing, BAFF provides additional predictive value for ABMR.

Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.

Cryptococcal meningitis has been described in immunocompromised patients, as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryptococcal control. We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in four current patients with cryptococcal meningitis and identified and tested 103 archived plasma/cerebrospinal fluid samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody-containing plasmas to inhibit GM-CSF signaling. We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis (PAP). Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the seven later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal PBMCs. This effect was limited to their IgG fraction. Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated PAP.

Adult-onset immunodeficiency in Thailand and Taiwan.

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection.

Patients with anti-IFN-γ autoantibodies have impaired IFN-γ signaling, leading to severe disseminated infections with intracellular pathogens, especially nontuberculous mycobacteria. Disease may be severe and progressive, despite aggressive treatment. To address the underlying pathogenic IFN-γ autoantibodies we used the therapeutic monoclonal rituximab (anti-CD20) to target patient B cells. All subjects received between 8 and 12 doses of rituximab within the first year to maintain disease remission. Subsequent doses were given for relapsed infection. We report 4 patients with refractory disease treated with rituximab who had clinical and laboratory evidence of therapeutic response as determined by clearance of infection, resolution of inflammation, reduction of anti-IFN-γ autoantibody levels, and improved IFN-γ signaling.

Determination of human anticytokine autoantibody profiles using a particle-based approach.

BACKGROUND: Anticytokine autoantibodies cause numerous human diseases, ranging from pure red cell aplasia to acquired immunodeficiencies. Rapid, simple, and affordable detection and monitoring of these antibodies is essential. We sought to develop a standardizable assay that is rapid, sensitive, and specific and able to simultaneously detect multiple anticytokine autoantibodies in small volumes (<10 µl). METHODS: We conjugated purified human cytokines to commercially available fluorescently labeled microspheres and tested them against sera from well-characterized subjects with at least one high-titer, disease-associated anticytokine autoantibody. RESULTS: Cytokine-conjugated microspheres efficiently and rapidly determined plasma concentration and IgG subclass of anticytokine autoantibodies in single or multiplex formats. CONCLUSION: This particle-based multiplex assay can reproducibly characterize anticytokine autoantibodies. This efficient and inexpensive approach to diagnosing and monitoring anticytokine autoantibodies has clinical applications.

Therapeutic effectiveness of a generic versus original meropenem in serious infections.

BACKGROUND: Meropenem plays a significant role in the current antimicrobial treatment of serious infections. Recently, generic meropenems have become widely available in Thailand. OBJECTIVE: Compare the effectiveness and safety ofa generic meropenem (Mapenem) with the original meropenem (Meronem) in clinical practice. MATERIAL AND METHOD: A retrospective cohort study was conducted in hospitalized patients with serious infections that had been treated with either the generic or the original meropenem in nine secondary- and tertiary-care hospitals nationwide. The treatment outcomes at days 3, 7, and 14 after the use ofmeropenem between the two groups were compared. RESULTS: Three hundred ninety seven patients with a mean (SD) age of 66.4 +/- 16.9 years were included. There were 228 (57.4%) males and 169 (42.6%) females. Two hundred and seven (52.1%) and 190 (47.9%) cases fell into the generic and original groups respectively. There were no significant differences regarding age, gender history of underlying disease, body weight, and ward of admission between the two groups. The majority ofpatients had presented with the respiratory tract (48.6%) and bloodstream infections (29.5%). The three most common causative bacteria were Pseudomonas aeruginosa, Acinetobacter baumannii, and extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. The distribution ofthe sites of infection, causative microorganisms, the dosage ofmeropenem, and duration oftreatment were similar between the two groups. The distribution of patients with complete resolution, improvement, stable, worse, diedfrom infection, and died from other causes were similar between the two groups at day 3, 7, and 14 ofmeropenem use (p > 0.05). The drugs were well-tolerated, and less than 2% of patients in both groups discontinued meropenem due to the adverse drug effects. CONCLUSION: The generic meropenem has a similar effectiveness in the treatment of serious bacterial infections when compared with original meropenem. Both formulations are well tolerated among patients with substantial comorbidities. Adverse drug effects that lead to drug discontinuation are uncommon.

A prospective study of ceftriaxone treatment in acute pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria.

BACKGROUND: Much controversy exists as to whether cephalosporin treatment is appropriate for infections caused by ESBL-producing organisms because no randomized controlled studies have been performed. OBJECTIVE: Evaluate the therapeutic outcomes of ceftriaxone treatment in acute pyelonephritis caused by ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. MATERIAL AND METHOD: The authors performed a prospective study in female patients hospitalized with acute pyelonephritis caused by ESBL-producing or ESBL-nonproducing E. coli, K. pneumoniae, or P. mirabilis in four hospitals in Thailand from 2004 to 2006. The clinical and microbiological outcomes were evaluated at 72 hours after empirical ceftriaxone treatment. RESULTS: One hundred eleven patients with the mean age of 65.29 years participated in this study. There were no differences in demographic and clinical characteristics and laboratory data between the ESBL-producing and ESBL-nonproducing groups except the higher rates of previous antibiotic use and urinary tract infection; and the lower frequency of costovertebral angle tenderness in the ESBL-producing group. Both clinical (65% and 93%) and microbiological (67.5% and 100%) responses at 72 hours after ceftriaxone treatment were poorer in the ESBL-producing group than in the ESBL-nonproducing group (p < 0.0002). CONCLUSION: To the authors' knowledge, this is the first prospective study to evaluate the outcomes of ceftriaxone treatment in acute pyelonephritis caused by ESBL-producing Enterobacteriaceae. The present study confirms that acute pyelonephritis in the female patients caused by ESBL-producing strains could not be treated with ceftriaxone.

Basal ganglia and brainstem encephalitis, optic neuritis, and radiculomyelitis in Epstein-Barr virus infection.

The neurologic complications of Epstein-Barr virus (EBV) infection are rare. We describe a healthy adult with acute EBV meningoencephalomyeloradiculitis. The clinical manifestations, a serologic study, and a dynamic change of EBV DNA in the cerebrospinal fluid with spontaneous recovery confirmed the diagnosis of EBV infection of the nervous system. In addition, we provide other clinical clues for suspicion of EBV infection in patients with encephalitis. These include bilateral basal ganglia and brainstem lesions on magnetic resonance imaging, optic neuritis, or involvement of all levels of the nervous system.