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.

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.

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 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.

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.

Mortality in Thai Nursing Homes Based on Antimicrobial-Resistant Enterobacterales Carriage and COVID-19 Lockdown Timing: A Prospective Cohort Study.

Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing homes.

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.

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.

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.

Quantitative PCR to Discriminate Between Pneumocystis Pneumonia and Colonization in HIV and Non-HIV Immunocompromised Patients.

Pneumocystis pneumonia (PCP) is an opportunistic infection that commonly occurs in immunocompromised individuals. A definite diagnosis of PCP can be made only when the organism is identified in a respiratory specimen. It remains unclear whether qPCR can differentiate patients with PCP from those with Pneumocystis jirovecii colonization. In this study, we retrospectively collected data from HIV and non-HIV patients during 2013-2019. A diagnosis of definite, probable PCP, or PCP excluded was made based on clinical criteria, radiological reports, and three standard laboratory staining methods with blinding to qPCR data. Data from qPCR that was performed to determine the fungal burden (DNA copies/µl) in the BAL specimens of 69 HIV and 286 non-HIV patients were then obtained and reviewed. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the upper and lower cut-off values for PCP diagnosis in HIV and non-HIV groups. In the non-HIV group, the lower cut-off value of 1,480 DNA copies/µl yielded a sensitivity of 100% (95% confidence interval [CI], 91.0-100), specificity of 72.9% (95% CI, 64.0-80.7), a positive predictive value (PPV) of 54.9% (95% CI, 47.6-62.1), and a negative predictive value (NPV) of 100% with Youden index of 0.73 for PCP diagnosis. In this group, the upper cut-off value of 9,655 DNA copies/µl showed the sensitivity of 100% (95% CI, 91.0-100) and specificity of 95.8% (95% CI, 90.4-98.6) with PPV of 88.6% (95% CI, 76.8-94.8) and a NPV of 100% with Youden index of 0.96 for PCP diagnosis. Regarding the HIV group, the lower cut-off value of 1,480 DNA copies/µl showed the sensitivity of 100% (95% CI, 92.5-100%) and specificity of 91.7% (95% CI, 61.5-99.8) with PPV of 97.9% (95% CI, 87.8-99.7) and a NPV of 100% with Youden index of 0.92 for PCP diagnosis. The sensitivity and specificity of the upper cut-off value of 12,718 DNA copies/µl in this group were 97.9% (95%CI, 88.7-100) and 100% (95%CI, 73.5-100), respectively. The values above the upper cut-off point had a PPV of 100% (95% CI, N/A) and a NPV of 92.3% (95% CI, 63.3-98.8) with Youden index of 0.98 for PCP diagnosis in the HIV group.

Nosocomial Fever in General Medical Wards: A Prospective Cohort Study of Clinical Characteristics and Outcomes.

PURPOSE: Nosocomial fever (NF) is a common sign of healthcare-associated infection; however, infection is not always followed up. We studied the etiology, clinical characteristics, and outcomes of nosocomial fever in hospitalized patients. PATIENTS AND METHODS: Between October 2019 and December 2020, we enrolled subjects from general medical wards who developed fever ≥48 hours after hospital admission or who were admitted with fever, defervesced, and then developed a fever ≥7 days later that was unrelated to the cause for admission. Subjects with NF underwent a comprehensive clinical evaluation and laboratory investigations. RESULTS: Eighty-six cases of NF were identified and completely followed, the mean age was 69.29 years, and 35 were male. Fifty-seven were from infectious etiologies, 28 from non-infectious etiologies, and one case was unable to be determined. Hospital-associated pneumonia (47.4%) and urinary tract infection (22.8%) were the most common infectious causes, and malignancy (17.8%) and large hematoma (14.3%) were the most common non-infectious causes. The median day of onset of NF following hospitalization was 12 (4.7-21.2) days. Acute physiology and chronic health evaluation II (APACHE II) score (14.70 vs 11.97, p = 0.02), sequential organ failure assessment (SOFA) scores (4 vs 2, p < 0.01), pertinent clinical findings (82.5% vs 42.9%, p < 0.01), blood urea nitrogen (BUN) (37.30 vs 21.10, p = 0.03) and creatinine (1.41 vs 0.97, p = 0.05) levels, and abnormal chest radiography (45.6% vs 3.6%, p < 0.01) had significant differences between infectious and non-infectious etiologies. Twenty-three subjects (26.7%) died. The presence of end-stage renal disease (ESRD) [OR 19.49 (1.77-214.18), p = 0.015], SOFA score >6 [OR 5.18 (1.04-25.90), p = 0.045], and abnormal chest radiography [OR 3.45 (1.16-10.29), p = 0.026] were significantly associated with mortality. CONCLUSION: Nosocomial infections, malignancy, and hematoma were the leading causes of NF. Severity scores, clinical findings, renal function tests, and chest radiography were distinguishing features between infectious and non-infectious etiologies. ESRD, high SOFA scores, and abnormal chest radiography were associated with mortality.

A novel droplet digital polymerase chain reaction for diagnosis of Pneumocystis pneumonia (PCP)-a clinical performance study and survey of sulfamethoxazole-trimethoprim resistant mutations.

Objectives To determine the performance of droplet digital polymerase chain reaction (ddPCR) assays in diagnosing Pneumocystis pneumonia (PCP), and to survey the sulfamethoxazole-trimethoprim (SMX-TMP) resistant mutations in our PCP cohort. Methods A prospective study was conducted from January 2017 to June 2018. Adult immunocompromised subjects with pneumonia were enrolled. Bronchoalveolar lavage fluid samples were obtained for standard microscopic testing and ddPCR to quantify the Pneumocystis MSG gene. DHPS and DHFR gene sequencings were performed to detect SMX-TMP resistance. Results Of 54 subjects, 12 had definite PCP, 7 had probable PCP, and 35 were non-PCP. In the PCP cohort, 10 (53%) had HIV infections. Using a cutoff value of ≥ 1.94 copies/µL, the ddPCR exhibited an overall sensitivity of 91.7% (61.5-99.8%) and specificity of 88.1% (74.4-96%). It showed a better performance when different cutoff values were used in subjects with HIV (≥ 1.80 copies/µL) and non-HIV (≥ 4.5 copies/µL). ROC curves demonstrated an AUC of 0.80 (95% CI, 0.56-1.0) for the HIV group, and 0.99 (95% CI, 0.95-1.0) for the non-HIV group. Of 16 PCP samples tested for DHPS- and DHFR-mutations, only DHPS mutations were detected (2). Most of the subjects, including those with DHPS mutations, demonstrated favorable outcomes. Conclusions The ddPCR exhibited a satisfactory diagnostic performance for PCP. Based on very limited data, the treatment outcomes of PCP did not seem to be affected by the DHPS mutations.

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.

Stenotrophomonas maltophilia Infections: Clinical Characteristics and Factors Associated with Mortality of Hospitalized Patients.

PURPOSE: To study the clinical characteristics and factors associated with mortality of patients who had Stenotrophomonas maltophilia infections. PATIENTS AND METHODS: We conducted a retrospective study to determine the clinical characteristics and factors associated with mortality for S. maltophilia infections among hospitalized adult patients at Siriraj Hospital. The clinical and microbiological data were collected from medical records December 2013-December 2016. RESULTS: Of 1221 subjects whose clinical samples grew S. maltophilia, 213 were randomly selected for chart review. One hundred patients with a true infection were analyzed. Their median age was 66 years; 47 were males; 46 were critically ill with a median APACHE II score of 18 (2-32); and 91 received antibiotic treatment, mainly with carbapenems (56%), before being diagnosed with a S. maltophilia infection. Pulmonary (53%) and bloodstream infections (25%) were the most common infections. The median length of hospitalization was 19 days before infection onset. The in-hospital mortality rate was 54%. The following factors were associated with mortality: a pre-existing respiratory infection (OR 6.28, 1.33-29.78; p.021); critical illness (OR 3.33, 1.45-7.62; p.005); multi-organ dysfunction (OR 2.44, 1.05-5.70; p.039); being on mechanical ventilation (OR 4.44, 1.90-10.39; p.001); concurrent immunosuppressive therapy (OR 2.67, 1.10-6.47; p.029); intravascular (OR 4.43, 1.79-10.92; p.001) and urinary catheterization (OR 4.83, 1.87-12.47; p.001); and serum albumin <3 g/dL (OR 4.13, 1.05-16.33; p.043). A multivariate analysis identified two independent factors associated with mortality: being on mechanical ventilation (OR 4.43, 1.86-10.59; p 0.001) and receiving concurrent immunosuppressive therapy (OR 2.26, 1.04-6.82; p 0.042). CONCLUSION: S. maltophilia can cause nosocomial infections with high mortality, particularly in patients with a prolonged hospitalization. Concurrent immunosuppressive therapy and being on mechanical ventilation are the independent factors associated with a fatal 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.

Lomentospora prolificans vertebral osteomyelitis with spinal epidural abscess in an immunocompetent woman: Case report and literature review.

Lomentospora prolificans is a rare cause of vertebral osteomyelitis. We report a case of L. prolificans thoracic vertebral osteomyelitis with spinal epidural abscess in a patient without apparent immunodeficiency. Clinical manifestations and radiographic findings could not distinguish from other etiologic agents. Treatment is also challenging because L. prolificans is usually resistant to antifungal agents. The patient underwent surgical debridement and has been receiving a prolonged combination of antifungal therapy to prevent an infection relapse.

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.

Epidemiology and risk factors of extensively drug-resistant Pseudomonas aeruginosa infections.

BACKGROUND: The incidence of nosocomial infections from extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide. We investigated the prevalence and factors associated with XDR-PA infections, including the factors that predict mortality. METHODS: We retrospectively studied a cohort of adult, hospitalized patients with P. aeruginosa (PA) infections between April and December 2014. RESULTS: Of the 255 patients with PA infections, 56 (22%) were due to XDR-PA, 32 (12.5%) to multidrug resistant Pseudomonas aeruginosa (MDR-PA), and 167 (65.5%) to non-MDR PA. Receiving total parenteral nutrition (adjusted OR [aOR] 6.21; 95% CI 1.05-36.70), prior carbapenem use (aOR 4.88; 95% CI 2.36-10.08), and prior fluoroquinolone use (aOR 3.38; 95% CI 1.44-7.97) were independently associated with the XDR-PA infections. All XDR-PA remained susceptible to colistin. Factors associated with mortality attributable to the infections were the presence of sepsis/septic shock (aOR 11.60; 95% CI 4.66-28.82), admission to a medical department (aOR 4.67; 95% CI 1.81-12.06), receiving a central venous catheter (aOR 3.78; 95% CI 1.50-9.57), and XDR-PA infection (aOR 2.73; 95% CI 1.05-7.08). CONCLUSION: The prevalence of XDR-PA infections represented almost a quarter of Pseudomonas aeruginosa hospital-acquired infections and rendered a higher mortality. The prompt administration of an appropriate empirical antibiotic should be considered when an XDR-PA infection is suspected.

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.

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.