Prevalence and risk factors of cytomegalovirus reactivation in critically Ill patients with COVID-19 pneumonia.

BACKGROUNDS: In critically ill patients with COVID-19, secondary infections are potentially life-threatening complications. This study aimed to determine the prevalence, clinical characteristics, and risk factors of CMV reactivation among critically ill immunocompetent patients with COVID-19 pneumonia. METHODS: A retrospective cohort study was conducted among adult patients who were admitted to ICU and screened for quantitative real-time PCR for CMV viral load in a tertiary-care hospital during the third wave of the COVID-19 outbreak in Thailand. Cox regression models were used to identify significant risk factors for developing CMV reactivation. RESULTS: A total of 185 patients were studied; 133 patients (71.9%) in the non-CMV group and 52 patients (28.1%) in the CMV group. Of all, the mean age was 64.7±13.3 years and 101 patients (54.6%) were males. The CMV group had received a significantly higher median cumulative dose of corticosteroids than the non-CMV group (301 vs 177 mg of dexamethasone, p<0.001). Other modalities of treatments for COVID-19 including anti-viral drugs, anti-cytokine drugs and hemoperfusion were not different between the two groups (p>0.05). The 90-day mortality rate for all patients was 29.1%, with a significant difference between the CMV group and the non-CMV group (42.3% vs. 24.1%, p = 0.014). Median length of stay was longer in the CMV group than non-CMV group (43 vs 24 days, p<0.001). The CMV group has detectable CMV DNA load with a median [IQR] of 4,977 [1,365-14,742] IU/mL and 24,570 [3,703-106,642] in plasma and bronchoalveolar fluid, respectively. In multivariate analysis, only a cumulative corticosteroids dose of dexamethasone ≥250 mg (HR = 2.042; 95%CI, 1.130-3.688; p = 0.018) was associated with developing CMV reactivation. CONCLUSION: In critically ill COVID-19 patients, CMV reactivation is frequent and a high cumulative corticosteroids dose is a significant risk factor for CMV reactivation, which is associated with poor outcomes. Further prospective studies are warranted to determine optimal management.

Molnupiravir versus favipiravir in at-risk outpatients with COVID-19: A randomized controlled trial in Thailand.

OBJECTIVES: Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. METHODS: In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. RESULTS: Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (-1.0%; Newcombe 95.2% CI: -2.4% to -0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). CONCLUSIONS: Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. THAI CLINICAL TRIALS REGISTRY ID: TCTR20230111009.

Increased platelet activation and lower platelet-monocyte aggregates in COVID-19 patients with severe pneumonia.

BACKGROUND: The increased procoagulant platelets and platelet activation are associated with thrombosis in COVID-19. In this study, we investigated platelet activation in COVID-19 patients and their association with other disease markers. METHODS: COVID-19 patients were classified into three severity groups: no pneumonia, mild-to-moderate pneumonia, and severe pneumonia. The expression of P-selectin and activated glycoprotein (aGP) IIb/IIIa on the platelet surface and platelet-leukocyte aggregates were measured prospectively on admission days 1, 7, and 10 by flow cytometry. RESULTS: P-selectin expression, platelet-neutrophil, platelet-lymphocyte, and platelet-monocyte aggregates were higher in COVID-19 patients than in uninfected control individuals. In contrast, aGPIIb/IIIa expression was not different between patients and controls. Severe pneumonia patients had lower platelet-monocyte aggregates than patients without pneumonia and patients with mild-to-moderate pneumonia. Platelet-neutrophil and platelet-lymphocyte aggregates were not different among groups. There was no change in platelet-leukocyte aggregates and P-selectin expression on days 1, 7, and 10. aGPIIb/IIIa expression was not different among patient groups. Still, adenosine diphosphate (ADP)-induced aGPIIb/IIIa expression was lower in severe pneumonia than in patients without and with mild-to-moderate pneumonia. Platelet-monocyte aggregates exhibited a weak positive correlation with lymphocyte count and weak negative correlations with interleukin-6, D-dimer, lactate dehydrogenase, and nitrite. CONCLUSION: COVID-19 patients have higher platelet-leukocyte aggregates and P-selectin expression than controls, indicating increased platelet activation. Compared within patient groups, platelet-monocyte aggregates were lower in severe pneumonia patients.

Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study.

BACKGROUND: Chronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV receiving ART. METHODS: A randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavastatin or placebo were investigated. RESULTS: A total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41-54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm3. The median duration of ATV/r use was 36 (24-48) months. Significant change in levels of basic fibroblast growth factor (FGF) between pitavastatin treatment and placebo at week 12 from baseline was observed (27.1 vs. 20.5 pg/mL; p=0.023). However, there were no significant changes from baseline of hs-CRP and other plasma cytokine levels at week 12 of pitavastatin or placebo. Regarding cellular markers, percentages of HLA-DR+CD38-CD4+ T cells and PD1+CD4+ T cells significantly decreased from baseline in PLHIV receiving pitavastatin for 12 weeks, as compared to placebo (- 0.27 vs. 0.02%; p=0.049 and - 0.23 vs. 0.23%; p=0.022, respectively). CONCLUSIONS: Pitavastatin treatment increases basic FGF levels, and lowers HLA-DR+CD38-CD4+ T cells, and PD1+CD4+ T cells. Further study on the effects of pitavastatin on preventing cardiovascular diseases in PLHIV should be pursued.

Detectable Duration of Viable SARS-CoV-2, Total and Subgenomic SARS-CoV-2 RNA in Noncritically Ill COVID-19 Patients: a Prospective Cohort Study.

Determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is important in guiding the infection control and differentiating between reinfection and persistent viral RNA. Although viral culture is the gold standard to determine viral infectivity, the method is not practical. We studied the kinetics of SARS-CoV-2 total RNAs and subgenomic RNAs (sgRNAs) and their potential role as surrogate markers of viral infectivity. The kinetics of SARS-CoV-2 sgRNAs compared to those of the culture and total RNA shedding in a prospective cohort of patients diagnosed with coronavirus disease 2019 (COVID-19) were investigated. A total of 260 nasopharyngeal swabs from 36 patients were collected every other day after entering the study until the day of viral total RNA clearance, as measured by reverse transcription PCR (RT-PCR). Time to cessation of viral shedding was in order from shortest to longest: by viral culture, sgRNA RT-PCR, and total RNA RT-PCR. The median time (interquartile range) to negativity of viral culture, subgenomic N transcript, and N gene were 7 (5 to 9), 11 (9 to 16), and 18 (13 to 21) days, respectively (P < 0.001). Further analysis identified the receipt of steroid as the factors associated with longer duration of viral infectivity (hazard ratio, 3.28; 95% confidence interval, 1.02 to 10.61; P = 0.047). We propose the potential role of the detection of SARS-CoV-2 subgenomic RNA as the surrogate marker of viral infectivity. Patients with negative subgenomic N RNA RT-PCR could be considered for ending isolation. IMPORTANCE Our study, combined with existing evidence, suggests the feasibility of the use of subgenomic RNA RT-PCR as a surrogate marker for SARS-CoV-2 infectivity. The kinetics of SARS-CoV-2 subgenomic RNA should be further investigated in immunocompromised patients.

Spontaneous tension hemothorax in a severe COVID-19 patient receiving ECMO therapy: The other side of COVID-19-associated coagulopathy.

As opposed to widely recognized Coronavirus Disease 2019 (COVID-19)-associated thrombotic events, the unusual but serious bleeding complications in COVID-19 patients are worth-mentioned. Here, we describe a 44-year-old man afflicted by COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) and submassive pulmonary embolism. The patient's condition initially improved with the prescription of ECMO, tocilizumab, and hemoadsorption, however, he later developed spontaneous tension hemothorax, which is considered rare but devastating in the setting of COVID-19. While the exact pathogenesis of COVID-19-associated bleeding events remains poorly understood, we aim to highlight the other aspect of coagulation dysfunction potentially caused by COVID-19.

SARS-CoV-2 RT-PCR positivity of individuals subsequent to completing quarantine upon entry into a country during a transmission-free period.

BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, many countries require travellers to undergo a reverse transcription-polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before travelling across borders. However, in persons having recovered from COVID-19, RT-PCR positivity can persist for an extended period. MATERIALS AND METHODS: We describe three cases who sought fit-to-fly certificates in Thailand during the period free of local transmission but were tested positive for RT-PCR for SARS-CoV-2. All had returned from a country with an active outbreak of COVID-19. Their clinical courses are described; positive nasopharyngeal swab samples were processed for viral isolation and whole-genome sequencing (WGS); and serology as well as neutralizing antibody were assessed. The contact tracing was carried out for determining evidence of indigenous transmission among close contacts of those three cases. RESULTS: All three cases were completely asymptomatic. Chest computerized tomography was not compatible with COVID-19 pneumonia; cell cultures failed to rescue replication-competent virus; WGS revealed fragmented viral genetic material from nasopharyngeal swab samples; and serological tests demonstrated stable levels of antibodies, together with the presence of neutralizing antibody, suggesting past infection with negligible transmission risk. Contact tracing identified no transmission in high-risk close contact individuals. CONCLUSION: RT-PCR positivity for SARS-CoV-2 might detect fragmented viral genome. Issuance of a travel certificate in these circumstances is problematic. Serology tests can help to define past infection. A practical acceptable set of guidelines for issuance of a COVID-19 safety travel certification is a necessity.

Missed opportunities for earlier diagnosis of HIV infection in people living with HIV in Thailand.

HIV testing is the first step to making people living with HIV (PLHIV) aware of their status. Thailand is among the countries where antiretroviral therapy is initiated in PLHIV at the lowest CD4 cell counts. We aimed to quantify and characterize missed opportunity (MO) for earlier diagnosis of HIV infection in PLHIV in Thailand. The medical records of adults who were newly diagnosed with HIV between 2019 and 2020 at the two tertiary hospitals in Thailand were reviewed. A hospital visit due to an HIV clinical indicator disease but an HIV test was not performed was considered an MO for HIV testing. Of 422 newly diagnosed PLHIV, 60 persons (14.2%) presented with at least one MO, and 20 persons (33.3%) had more than one MO. In PLHIV with MO, the median (interquartile range) time between the first MO event and HIV diagnosis was 33.5 (7-166) days. The three most common clinical manifestations that were missed were skin manifestations (25.0%), unexplained weight loss (15.7%), and unexplained lymphadenopathy (14.3%). Anemia was a factor associated with MO for HIV diagnosis [odds ratio (OR) 2.24, 95% confidence interval (CI) 1.25-4.35; p = 0.018]. HIV screening reduced the risk of MO for HIV diagnosis (OR 0.53 95% CI 0.29-0.95; p = 0.032). In conclusion, MOs for earlier diagnosis of HIV infection occurred in both participating hospitals in Thailand. Skin manifestations were the most common clinical indicator diseases that were missed. HIV testing should be offered for patients with unexplained anemia. Campaigns for HIV screening tests should be promoted.

Anti-HIV serological test algorithms to reduce false-positive and inconclusive results for low HIV prevalence and resource-limited areas.

A false-positive anti-human immunodeficiency virus (HIV) test result can have devastating consequences. Sequential HIV serological testing is a strategy that could be applied in resource-limited settings to reduce false-positive results when a nucleic acid test is not affordable. We aimed to compare the results of sequential anti-HIV testing algorithms recommended by the national guidelines and our hospital algorithm in the setting of low HIV prevalence. We retrospectively reviewed individuals whose anti-HIV tested positive by Architect HIV Ag/Ab Combo with a signal/cut-off ratio of 1.00-20.00 between January 2015 and June 2016 at a university hospital in Bangkok, Thailand. A total of 111,224 samples were requested for anti-HIV tests during the study period. Sixty-six adults and nine children/adolescents met the inclusion criteria of this study. Compared to the national guidelines, our hospital HIV diagnosis algorithm could identify two individuals with false-positive anti-HIV tests and a reduction of inconclusive diagnoses from 45 to one adult cases (p <.001). It also eliminated inconclusive diagnoses in four non-infected children with HIV-negative mothers. Our hospital HIV diagnosis algorithm can reduce the number of HIV misdiagnoses of serological tests in an area with low HIV prevalence. The sequential HIV serological test algorithms should be reviewed and evaluated in each institute.

SARS-CoV-2 neutralizing antibodies decline over one year and patients with severe COVID-19 pneumonia display a unique cytokine profile.

OBJECTIVES: As coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity. METHODS: This study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups. RESULTS: Peak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups. CONCLUSIONS: The study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Mice Immunized with the Vaccine Candidate HexaPro Spike Produce Neutralizing Antibodies against SARS-CoV-2.

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistic-friendly are critically needed for global equity, especially for middle- to low-income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported using the receptor-binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, named HexaPro, has been shown to possess two RBD in the "up" conformation, due to its physical property, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for the SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminum hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. Also, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.

The association between body mass index and severity of Coronavirus Disease 2019 (COVID-19): A cohort study.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) has become a worst pandemic. The clinical characteristics vary from asymptomatic to fatal. This study aims to examine the association between body mass index (BMI) levels and the severity of COVID-19. METHODS AND STUDY DESIGN: A cohort study included 147 adult patients with confirmed COVID-19 were categorized into 4 groups by BMI levels on admission: <18.5 (underweight), 18.5-22.9 (normal weight), 23.0-24.9 (overweight), and ≥25.0 kg/m2 (obese). Rates of pneumonia, severe pneumonia, acute kidney injury (AKI), and ICU stay during hospitalization across BMI group was determined. Logistic regression analysis was used to determine the association between BMI and severe pneumonia. RESULTS: Of the totals, patients having a BMI <18.5, 18.5-22.9, 23.0-24.9, and ≥25.0 kg/m2 were 12.9%, 38.1%, 17.7%, and 31.3%, respectively. The rates of pneumonia and severe pneumonia tended to be higher in patients with higher BMI, whereas the rates of AKI and ICU stay were higher in patients with BMI <18.5 kg/m2 and ≥ 25 kg/m2, when compared to patients with normal BMI. After controlling for age, sex, diabetes, hypertension and dyslipidemia in the logistic regression analysis, having a BMI ≥25.0 kg/m2 was associated with higher risk of severe pneumonia (OR 4.73; 95% CI, 1.50-14.94; p = 0.003) compared to having a BMI 18.5-22.9 kg/m2. During admission, elevated hemoglobin and alanine aminotransferase levels on day 7 and 14 of illness were associated with higher BMI levels. In contrast, rising of serum creatinine levels was observed in underweight patients on days 12 and 14 of illness. CONCLUSIONS: Obesity in patients with COVID-19 was associated with severe pneumonia and adverse outcomes such as AKI, transaminitis and ICU stay. Underweight patients should be closely monitored for AKI. Further studies in body composition are warranted to explore the links between adiposity and COVID-19 pathogenesis.

Clinical features of adult patients with a definite diagnosis of central nervous system tuberculosis in an endemic country: A 13-year retrospective review.

RATIONALE: Clinical features of central nervous system tuberculosis (CNS-TB) are nonspecific. The decision for treatment of the disease in an endemic area is challenging. OBJECTIVES: We aimed to study predictive factors for a definite diagnosis and outcome of patients with CNS-TB. METHODS: A case-control study was performed in adults with a provisional diagnosis of CNS-TB in Thailand to determine predictive factors for a definite diagnosis of CNS-TB. Predictive factors for a definite diagnosis of CNS-TB were analyzed by multivariable logistic regression analysis. Factors associated with two-year mortality after the diagnosis of definite CNS-TB were determined using a cox regression analysis. MEASUREMENTS AND MAIN RESULTS: A total of 114 patients received a provisional diagnosis of CNS-TB during the study period. A median (interquartile range) age was 40.8 (31.7-55.4) years, and 75 patients (65.8%) were male. Of these, 66 cases (57.9%) had definite CNS-TB, and 43 cases (38.4%) had HIV coinfection. By logistic regression, age, confusion, and nausea/vomiting were associated with definite CNS-TB (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.93-0.99; p = 0.015, OR 2.86, 95% CI 1.03-7.94; p = 0.044, and OR 0.30, 95% CI 0.11-0.82; p = 0.019, respectively). In patients with definite CNS-TB, age and HIV coinfection were associated with two-year mortality (hazard ratio [HR] 1.07, 95% CI 1.01-1.13; p = 0.022, and HR 11.81, 95% CI 2.09-66.78; p = 0.005, respectively). CONCLUSIONS: Younger age, confusion, and absence of nausea/vomiting are predictive factors of a definite diagnosis of CNS-TB. In patients with definite CNS-TB, older age and HIV coinfection are associated with higher mortality. The results of this study might be helpful for the management of suspected CNS-TB cases as well as predicting the prognosis of CNS-TB cases in an endemic area.

Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration.

BACKGROUND: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. MATERIALS AND METHODS: We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. RESULTS: We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. CONCLUSIONS: Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT04122222.

Epidemiology of carbapenem-resistant Enterobacteriaceae: a 5-year experience at a tertiary care hospital.

PURPOSE: The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing worldwide. Ertapenem resistance is mediated by non-carbapenemase mechanisms, and has less of an effect on susceptibility to imipenem and meropenem. This study aimed to study the epidemiology of CRE, and to compare risk factors and related mortality between non-susceptibility to ertapenem alone Enterobacteriaceae (NSEE), with non-susceptibility to other carbapenems (imipenem, meropenem, or doripenem) Enterobacteriaceae (NSOCE) at a tertiary care hospital in Thailand. METHODS: All CRE isolated were identified between December 2011 and December 2016. Quarterly incidence rate was estimated. Hospital-wide carbapenem consumption was calculated as defined daily doses (DDD). Relationships between hospital-wide carbapenem consumption and incidence of CRE were tested. Factors associated with NSEE and NSOCE, and risk factors associated with 14- and 30-day mortality in patients with CRE infection were determined. RESULTS: The quarterly CRE incidence increased significantly from 3.37 per 100,000 patient-days in the last quarter of 2011 to 32.49 per 100,000 patient-days in the last quarter of 2016. (P for trend <0.001). Quarterly hospital-wide carbapenem consumption increased 1.58 DDD per 1,000 patient-days (P for trend=0.004). The Poisson regression showed the expected increase of CRE incidence was 1.02 per 100,000 patient-days for a 1 DDD per 1,000 patient-days increase in carbapenem consumption (P<0.001). There were 40 patients with NSEE and 134 patients with NSOCE in the 5-year study period. The NSEE group had significantly lower carbapenem exposure compared with the NSOCE group (adjusted odds ratio: 0.25; P=0.001). No difference in 14-day and 30-day all-cause mortality between the two groups was observed. CONCLUSION: The incidence of CRE has risen significantly at our institution. Previous carbapenem use was associated with NSOCE. This hospital-wide carbapenem use was significantly associated with the increasing incidence of CRE.

Integrated therapy for HIV and cryptococcosis.

Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.

Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma.

Tuberculosis (TB) is a serious infectious disease that spreads globally. The ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been rarely reported. Here, we described a 38-year-old Thai man presenting with panophthalmitis of the right eye. Further investigation showed that he had concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well as HIV infection, with a CD4 cell count of 153 cells/mm(3). Despite the initial response to antituberculous agents, the disease had subsequently progressed and enucleation was required. The pathological examination revealed acute suppurative granulomatous panophthalmitis with retinal detachment. Further staining demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium tuberculosis were obtained from tissue culture. He was treated with antiretroviral agents for HIV infection and 12 months of antituberculous agents. Clinicians should be aware of the possibility of TB in the differential diagnosis of endophthalmitis and panophthalmitis, especially in regions where TB is endemic.

Resistance of monocyte to HIV-1 infection is not due to uncoating defect.

Freshly isolated blood monocytes show an early postentry block to in vitro HIV-1 infection. Differentiation into monocyte-derived macrophages (MDMs) is required to allow HIV replication in this cell type. In this study, we investigated whether the resistance of monocyte to HIV infection stemmed from uncoating defect. Monocyte and MDM lysates induced HIV-1 core uncoating to a comparable degree. This suggests that monocyte lacks a factor(s) essential for viral reverse transcription and/or contains a factor(s) interfering with this step.

Compositional bias and size of genomes of human DNA viruses.

Genomes of 144 human DNA viruses were analyzed in the aspect of their compositional asymmetry. DNA viruses were divided into two groups according to their genome sizes. The analysis revealed that the level of guanine and cytosine (GC content) in the coding sequences of small genome DNA viruses was significantly lower than that of large genome DNA viruses. Because small genome viruses replicate their genomes using cellular enzymes, while large genome viruses use their own enzymes for genome replication, the two groups of viruses may be under different mutational bias and/or selection pressure. In these viruses, GC content at the third codon position correlated with GC content at the first and second codon position. However, the relationship in small genome DNA viruses was weaker than that in large genome DNA viruses, suggesting that their genome composition may be more strongly influenced by codon usage preference or restriction on amino acid composition.