Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study.

BACKGROUND: Central nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient's immune status alters the clinical manifestations and treatment outcomes of CNS TB. METHODS: Between January 2007-December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID). RESULTS: Of 310 subjects, 160 (51.6%) were in the ID group-132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status -HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups. CONCLUSIONS: TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Brain abscess mimicking acute stroke syndrome caused by dual Filifactor alocis and Porphyromonas gingivalis infections: A case report.

This case report is about a woman who had a brain abscess in the left parietal lobe that atypically presented as acute stroke-like syndrome. Pus samples from brain abscess aspiration revealed the periodontal pathogens Porphyromonas gingivalis and Filifactor alocis. After dental health care and 8 weeks of combined antimicrobial therapy, the patient recovered completely.

Epidemiology, clinical characteristics, and treatment outcomes of patients with COVID-19 at Thailand's university-based referral hospital.

BACKGROUND: The epidemiology and outcomes of COVID-19 patients in Thailand are scarce. METHODS: This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020. RESULTS: The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive. CONCLUSIONS: The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.

A case report of Talaromyces marneffei Oro-pharyngo-laryngitis: a rare manifestation of Talaromycosis.

BACKGROUND: The incidence of Taralomyces marneffei infection in HIV-infected individuals has been decreasing, whereas its rate is rising among non-HIV immunodeficient persons, particularly patients with anti-interferon-gamma autoantibodies. T. marneffei usually causes invasive and disseminated infections, including fungemia. T. marneffei oro-pharyngo-laryngitis is an unusual manifestation of talaromycosis. CASE PRESENTATION: A 52-year-old Thai woman had been diagnosed anti-IFNÉ£ autoantibodies for 4 years. She had a sore throat, odynophagia, and hoarseness for 3 weeks. She also had febrile symptoms and lost 5 kg in weight. Physical examination revealed marked swelling and hyperemia of both sides of the tonsils, the uvula and palatal arches including a swelling of the epiglottis, and arytenoid. The right tonsillar biopsy exhibited a few intracellular oval and elongated yeast-like organisms with some central transverse septum seen, which subsequently grew a few colonies of T. marneffei on fungal cultures. The patient received amphotericin B deoxycholate 45 mg/dayfor 1 weeks, followed by oral itraconazole 400 mg/day for several months. Her symptoms completely resolved without complication. CONCLUSION: In patients with anti-IFN-É£ autoantibodies, T. marneffei can rarely cause a local infection involving oropharynx and larynx. Fungal culture and pathological examination are warranted for diagnosis T. marneffei oro-pharyngo-laryngitis. This condition requires a long term antifungal therapy.

Undiagnosed Cryptococcus gattii meningitis leading to subsequent ventriculoperitoneal shunt infection in a patient with symptoms of normal pressure hydrocephalus: case report and literature review.

BACKGROUND: Cryptococcus gattii is known to be an etiologic agent of human cryptococcosis, particularly in immunocompetent persons. C. gattii infection usually involves the central nervous system, the respiratory tract, or may be disseminated. Here we report an atypical manifestation of C. gattii infection in a patient who had C. gattii meningitis complicating the ventriculoperitoneal (VP) shunt infection and concurrent infected intraabdominal VP shunt pseudocyst. CASE PRESENTATION: A 66-year-old Thai female was initially diagnosed with normal pressure hydrocephalus (NPH) and underwent programmable VP shunt placement. However, she still suffered from recurrent communicating hydrocephalus with in-place VP shunt, and later developed recurrent gait impairment, chronic abdominal pain and abdominal mass. Radiological studies demonstrated recurrent hydrocephalus and a very large intraabdominal VP shunt pseudocyst. C. gattii was isolated from both the cerebrospinal fluid and the pseudocyst aspiration. C. gattii meningitis complicating the VP shunt infection and concurrent infected intraabdominal VP shunt pseudocyst was diagnosed. Prolonged antifungal therapy, removal of the infected VP shunt with subsequent implant of a new shunt provided a good outcome. CONCLUSION: Chronic C. gattii meningitis should be aware in a patient presenting with normal pressure hydrocephalus. Under-diagnosed cryptococcal meningitis following VP shunt insertion for treating the hydrocephalus can render a complicated VP shunt infection including infected VP shunt pseudocyst.

Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-ß-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial.

BACKGROUND: Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-ß-lactamase-producing Enterobacteriaceae. METHODS: We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued. RESULTS: During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05). CONCLUSIONS: Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First patient enrolled on 27 June 2011.

Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

BACKGROUND: Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. METHODS: We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. RESULTS: A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p < .001). Implant removal was associated with improved favorable outcomes at 6 months (OR 5.96; 95% CI 1.88-18.88; p < .01) and 12 months (OR 3.96; 95% CI 1.15-13.71; p = .03) after the infection. CONCLUSIONS: RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

Performance of the Cryptococcal Antigen Lateral Flow Assay in Non-HIV-Related Cryptococcosis.

The cryptococcal antigen lateral flow assay (CrAg LFA) was evaluated for the diagnosis of cryptococcosis in HIV-negative patients. The sensitivity was excellent, suggesting that this assay can replace conventional testing based on latex agglutination (LA). CrAg LFA and LA titers were correlated but were not directly comparable, with implications for conversion between assays.

Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing.

OBJECTIVES: Colistin, administered intravenously as its inactive prodrug colistin methanesulphonate (CMS), is being increasingly used. However, there is very limited information available on the impact of haemodialysis (HD) on the pharmacokinetics of CMS and formed colistin. PATIENTS AND METHODS: A single 30 min intravenous dose of CMS (150 mg of colistin base activity) was administered to 10 patients undergoing HD. HD was performed from 1.5 to 5.5 h after the start of the CMS infusion. Serial blood samples were collected over 50 h, additional blood samples pre- and post-dialysis membrane at three timepoints during HD, dialysate samples at four timepoints during HD, and a cumulative urine sample over 24 h. CMS and colistin were determined by HPLC. Population modelling and determination of HD clearance by multiple methods was conducted. RESULTS: The average amount of CMS recovered in the dialysate was 30.6% of the dose administered. The concentrations of CMS and colistin in the plasma and the amounts of CMS recovered in the dialysate were well described by the population disposition model. The clearance of CMS by dialysis as estimated by population analysis based on systemic plasma concentrations and amounts in the dialysate was 4.26 L/h (26% coefficient of variation). The dialysis clearance determined from the pre- and post-membrane plasma concentrations was 5.67 L/h (21%) for CMS and 3.99 L/h (44%) for colistin. Thus, CMS clearance by dialysis from trans-cartridge extraction was ∼30% higher than when calculated based on the amount in dialysate, suggesting adsorption to the membrane. CONCLUSIONS: Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.

PREVALENCE AND FACTORS ASSOCIATED WITH MULTIDRUG-RESISTANT TUBERCULOSIS AT SIRIRAJ HOSPITAL, BANGKOK, THAILAND.

The objective of this study was to determine the prevalence and factors associated with multidrug-resistant tuberculosis (MDR-TB) at Siriraj Hospital, Bangkok, Thailand. We conducted a retrospective unmatched case-control study of patients clinically diagnosed and microbiologically confirmed to have tuber- culosis (TB) at Siriraj Hospital from 2010 to 2012. Patient characteristics, clinical data, microbiological findings, outcomes and drug susceptibilities were recorded. A total of 188 subjects were included in the study; 52.1% (98) were males; the mean age was 48.9 years. Subjects were categorized into one of two groups, as follows: non-MDR-TB (141 patients) and MDR-TB (47 patients). The prevalence of MDR- TB was 2.6%. Co-morbidities of study subjects included diabetes mellitus (16.5%), HIV infection (16%) and cancer (5.9%). One hundred thirty-one patients (69.7%) had pulmonary TB. Factors significantly associated with MDR-TB were age < 65 years (OR = 6.94; 95% CI: 1.02-45.49; p = 0.048), history of TB (OR = 51.86; 95% CI: 12.35-217.79; p < 0.001), HIV co-infection (OR = 3.83; 95% CI: 1.02-14.38; p = 0.047) and alcohol consumption (OR = 3.90; 95% CI: 1.03-14.72; p = 0.045). Of the 146 patients for whom a clinical outcome was available, 51 (34.9%) had an unfavorable outcome. Poor compliance (OR = 13.51; 95% CI: 3.97-45.45; p < 0.001) and previous history of TB (OR = 8.16; 95% CI: 1.76-37.73; p = 0.007) were associated with an unfavorable outcome. MDR-TB was significantly associated with: patients aged < 65 years, those with a previous history of TB, those with HIV co-infection and those who drank alcohol. These factors should be kept in mind when treating TB patients at Siriraj Hospital, Thailand.

Pharmacokinetics of colistin methanesulfonate and formed colistin in end-stage renal disease patients receiving continuous ambulatory peritoneal dialysis.

Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD. Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity [CBA]) over 30 min. Serial blood and dialysate samples, and cumulative urine where applicable, were collected over 25 h. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted. The total body clearance of CMS (excluding CAPD clearance) was 1.77 liters/h (44%) [population mean (between-subject variability)], while CAPD clearance was 0.088 liter/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, the total clearance/fraction of CMS metabolized to colistin (fm) (excluding CAPD clearance) was 2.74 liters/h (50%), the CAPD clearance was 0.101 liter/h (34%), and the mean terminal half-life was 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/liter. Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients.

Multiplex Gastrointestinal Panel Testing in Hospitalized Patients With Acute Diarrhea in Thailand.

Background: Multiplex gastrointestinal (GI) panel testing is widely used for outpatient diagnosis of diarrhea. However, the clinical practicality of multiplex testing in hospitalized diarrheal subjects has not yet been thoroughly elucidated. Methods: We enrolled hospitalized subjects with acute diarrhea. The subjects' stool samples were collected in triplicate; 1 sample was tested using traditional diagnoses, and the other 2 were tested using Allplex (AP) and FilmArray (FA) GI panel testing. Clinical data were reviewed and analyzed. Results: Of the 199 subjects, 92 (46.5%) were male, and the mean age was 66.3 years. The median (interquartile range) onset of diarrhea was 6 (2--14) days after hospitalization. One hundred fifty-one patients (75.9%) had sepsis, and 166 (83.4%) had received prior or were receiving current antimicrobial therapy. Positive stool cultures were obtained from 4/89 (4.5%), and Clostridioides difficile toxin gene tests were positive in 14/188 (7.4%) patients. AP and FA multiplex tests were positive for GI pathogens in 49/199 (24.6%) and 40/199 (20.1%), respectively. The target most frequently detected by AP was Aeromonas spp. Both assays commonly detected enteropathogenic E. coli (EPEC), C. difficile toxin gene, and Salmonella spp.; neither assay detected pathogens in 75.4% and 79.9%. Fever (odds ratio [OR], 2.05; 95% CI, 1.08-3.88; P = .028), watery diarrhea (OR, 2.69; 95% CI, 1.25-5.80; P = .011), and antimicrobial therapy (OR, 2.60; 95% CI, 1.18-5.71; P = .018) were independent factors associated with the negative multiplex test result. Conclusions: Multiplex GI panel testing effectively detects enteric pathogens associated with diarrhea in hospitalized subjects. The etiology remains undiagnosed in >75% of cases. Factors contributing to negative test results should be considered before implementing the tests.

Severe Complications of Uterine Dehiscence Post-Lower Segment Cesarean Section: A Case Report Emphasizing the Importance of Timely Diagnosis and Intervention.

BACKGROUND Uterine dehiscence, an infrequent event often mistaken for uterine rupture, is rarely linked to post-cesarean section procedures and can result in severe complications, notably puerperal sepsis. In this report, we present a case that exemplifies the onset of puerperal sepsis and the emergence of intra-abdominal abscesses attributed to uterine dehiscence following a lower segment cesarean section (LSCS). CASE REPORT Our patient, a 28-year-old woman in her third pregnancy, underwent LSCS 1 week earlier. Subsequently, she returned to the hospital with lower abdominal pains, fever, and malodorous vaginal discharge. Computed tomography (CT) scan of whole abdomen verified uterine dehiscence and pus collection at the subhepatic region and right paracolic gutter. After referral to a specialized hospital, laboratory findings indicated an elevated white blood cell count and alkaline phosphatase levels, and coagulation abnormalities. She underwent an exploratory laparotomy, which unveiled uterine dehiscence, abscesses, and adhesions, necessitating a total abdominal hysterectomy and abdominal toileting. Pus culture analysis identified the presence of E. coli, which was susceptible to ampicillin/sulbactam. Complications were encountered after surgery, including wound dehiscence and pus re-accumulation. Successful management involved vacuum dressings and percutaneous drainage. Eventually, her condition improved and she was discharged, without additional complications. CONCLUSIONS This report underscores the importance of considering cesarean scar dehiscence as a diagnosis in women with previous cesarean deliveries who present during subsequent pregnancies with symptoms such as abdominal pain or abdominal sepsis. Diagnostic tools, such as CT, play pivotal roles, and the timely performance of an exploratory laparotomy is paramount when suspicion arises.

Disseminated Mycobacterium avium and recurrent Salmonella group D infection in a patient with autoantibodies to interferon-gamma.

We reported a case of a 40-year-old woman who presented with prolonged fever for 1 month, left sternoclavicular arthritis, anemia, multiple cervical lymphadenopathy and hepatosplenomegaly. She had a previous history of recurrent Salmonella group D septicemia. Computed tomography of her chest and abdomen revealed left sternoclavicular (SC) arthritis, left subscapular collections, hepatosplenomegaly, and multiple hypodensed lesions in the spleen. Blood, synovial fluid and bone marrow for mycobacterial cultures identified Mycobacterium avium by real-time PCR and reverse hybridization. Cell mediated immunodeficiency investigations were strongly positive for autoantibodies to interferon-gamma (IFN-gamma) by ELISA technique. During the third week of antimycobacterial therapy, she developed an acute generalized pustular eruption. Skin biopsy showed leukocytoclastic vasculitis; drug allergy was suspected. The pustular eruption resolved with steroid treatment and discontinuation of levofloxacin and clarithromycin. She was discharged home after 8 weeks of hospitalization with azithromycin, rifampicin and ethambutol.

Fatal liver mass rupture in a common-variable-immunodeficiency patient with probable nodular regenerating hyperplasia.

BACKGROUND: Nodular regenerating hyperplasia (NRH) is the most common liver involvement in common variable immunodeficiency (CVID). Most patients are asymptomatic with gradually increasing alkaline phosphatase (ALP) and mildly elevated transaminase enzymes over the years. We report the first case of fatal liver mass rupture in a CVID patient with probable NRH. CASE PRESENTATION: A 24-year-old man was diagnosed with CVID at the age of 1.25 years. Genetic testing revealed a transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI) mutation. He had been receiving intravenous immunoglobulin (IVIg) replacement therapy ever since then. The trough level of serum IgG ranged between 750-1200 mg/dL. However, he still had occasional episodes of lower respiratory tract infection until bronchiectasis developed. At 22 years old, computed tomography (CT) chest and abdomen as an investigation for lung infection revealed incidental findings of numerous nodular arterial-enhancing lesions in the liver and mild splenomegaly suggestive of NRH with portal hypertension. Seven months later, he developed sudden hypotension and tense bloody ascites. Emergency CT angiography of the abdomen showed NRH with intrahepatic hemorrhage and hemoperitoneum. Despite successful gel foam embolization, the patient died from prolonged shock and multiple organ failure. CONCLUSIONS: Although CVID patients with NRH are generally asymptomatic, late complications including portal hypertension, hepatic failure, and hepatic rupture could occur. Therefore, an evaluation of liver function should be included in the regular follow-up of CVID patients.

A multiplex pneumonia panel for diagnosis of hospital-acquired and ventilator-associated pneumonia in the era of emerging antimicrobial resistance.

Background: Antimicrobial resistance (AMR), including multidrug (MDR) and extensively drug-resistant (XDR) bacteria, is an essential consideration in the prevention and management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). In the AMR era, the clinical utility of the BioFire FilmArray Pneumonia Panel Plus (BFPP) to diagnose HAP/VAP has not been thoroughly evaluated. Methods: We enrolled adult hospitalized patients with HAP or VAP at Siriraj Hospital and Saraburi Hospital from July 2019-October 2021. Respiratory samples were collected for standard microbiological assays, antimicrobial susceptibility testing (AST), and the BFPP analysis. Results: Of 40 subjects, 21 were men. The median duration of HAP/VAP diagnoses was 10.5 (5, 21.5) days, and 36 endotracheal aspirate and 4 sputum samples were collected. Standard cultures isolated 54 organisms-A. baumannii (37.0%), P. aeruginosa (29.6%), and S. maltophilia (16.7%). 68.6% of Gram Negatives showed an MDR or XDR profile. BFPP detected 77 bacterial targets-A. baumannii 32.5%, P. aeruginosa 26.3%, and K. pneumoniae 17.5%. Of 28 detected AMR gene targets, CTX-M (42.5%), OXA-48-like (25%), and NDM (14.3%) were the most common. Compared with standard testing, the BFPP had an overall sensitivity of 98% (88-100%), specificity of 81% (74-87%), positive predictive value of 60% (47-71%), negative predictive value of 99% (96-100%), and kappa (κ) coefficient of 0.64 (0.53-0.75). The concordance between phenotypic AST and detected AMR genes in Enterobacterales was 0.57. There was no concordance among A. baumannii, P. aeruginosa, and S. aureus. Conclusions: The BFPP has excellent diagnostic sensitivity to detect HAP/VAP etiology. The absence of S. maltophilia and discordance of AMR gene results limit the test performance.

The burden of carbapenem-resistant Enterobacterales infection in a large Thai tertiary care hospital.

Background: Carbapenem-resistant Enterobacterales (CRE) are resistant to several other classes of antimicrobials, reducing treatment options and increasing mortality. We studied the clinical characteristics and burden of hospitalized adult patients with CRE infections in a setting where treatment options are limited. Methods: A retrospective cohort study included adult inpatients between January 2015-December 2019 at Siriraj Hospital in Bangkok, Thailand. Clinical and microbiological data were reviewed. Results: Of 420 patients with CRE infections, the mean age was 65.00 ± 18.89 years, 192 (45.72%) were male, and 112 (26.90%) were critically ill. Three hundred and eighty (90.48%) had Klebsiella pneumoniae, and 40 (9.52%) had Escherichia coli infections. The mean APACHE II score was 14.27 ± 6.36. Nearly half had previous hospitalizations (48.81%), 41.2% received antimicrobials, and 88.1% had undergone medical procedures before the onset of infection. The median time of onset of CRE infection was 16 days after admission. Common sites of infection were bacteremia (53.90%) and pneumonia (45.47%). Most CRE-infected patients had septic shock (63.10%) and Gram-negative co-infections (62.85%). Colistin (29.95%) and non-colistin (12.91%) monotherapies, and colistin-based (44.78%) and non-colistin-based (12.36%) combination therapies were the best available antimicrobial therapies (BAAT). The median length of hospitalization was 31 days, and the median hospitalization cost was US$10,435. The in-hospital mortality rate was 68.33%. Septic shock [adjusted odds ratio (aOR) 10.73, 5.65-20.42, p <0 .001], coinfection (aOR 2.43, 1.32-4.47, p = 0.004), mechanical ventilation (aOR 2.33, 1.24-4.36, p = 0.009), and a high SOFA score at onset (aOR 1.18, 1.07-1.30, p <0 .001) were associated with mortality. Conclusion: CRE infection increases mortality, hospital stays, and healthcare costs. A colistin-based regimen was the BAAT in this study. Therefore, newer antimicrobial agents are urgently needed.

Corrigendum: The first molecular genotyping of Naegleria fowleri causing primary amebic meningoencephalitis in Thailand with epidemiology and clinical case reviews.

[This corrects the article DOI: 10.3389/fcimb.2022.931546.].

The First Molecular Genotyping of Naegleria fowleri Causing Primary Amebic Meningoencephalitis in Thailand With Epidemiology and Clinical Case Reviews.

Primary amebic meningoencephalitis (PAM) is a rare and fatal central nervous system infection caused by Naegleria fowleri, a free-living amoeba found in the environment. To date, eight pathogenic N. fowleri genotypes have been reported worldwide. We aimed to explore the genotypes of N. fowleri that cause primary amebic meningoencephalitis in Thailand. In 2021, the 17th PAM case was reported, and a retrospective literature search of PAM cases in Thailand from 1982 through April 2021 was performed. Phylogenetic and genotyping analyses of the two mitochondrial (12S rRNA and 16S rRNA) and nuclear (ITS1 and 5.8s rRNA) genes of N. fowleri were performed on four available clinical isolates. Based on the mitochondrial and nuclear genes, N. fowleri genotype T3 was found to cause PAM in three out of four cases. However, disagreement between the genotype based on the mitochondrial and nuclear genes was found in one of the PAM cases, in which the 12S rRNA locus suggested the causative genotype as T1, while the ITS1 implied genotype T4. The discrepancy between the mitochondrial and nuclear genome was previously observed, which suggests the possible horizontal gene transfer among N. fowleri species. Based on the ITS1 gene, two N. fowleri genotypes, T3 and T4, were found to be the genotypes causing PAM in this study. In addition, N. fowleri genotype T2 was previously reported in a traveler who was infected in Thailand. Thus, at least three genotypes (T2, T3, and T4) of N. fowleri are found to be associated with PAM in Thailand.