Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.

Mycobacterium abscessus bacteremia after receipt of intravenous infusate of cytokine-induced killer cell therapy for body beautification and health boosting.

BACKGROUND: We report the first series of Mycobacterium abscessus bacteremia after cytokine-induced killer cell therapy for body beautification and health boosting. METHODS: The clinical manifestations, laboratory and radiological investigations, cytokine/chemokine profiles, and outcomes were described and analyzed. RESULTS: Four patients were admitted, and 3 patients had septic shock. Chest radiographs showed pulmonary infiltrates in all patients. Three patients developed peripheral gangrene, and 1 patient required lower limb and finger amputations. Patient 1 also developed disseminated infection including meningitis and urinary tract infection. Postmortem examination of patient 1 showed focal areas of pulmonary hemorrhage and diffuse alveolar damage, splenic infarct, adrenal necrosis, and hemorrhage, and acid-fast bacilli (AFB) were seen in the lung, liver, kidney, and adrenal gland. Patient 2 developed inguinal granulomatous lymphadenitis about 40 days after onset of lower limb gangrene. Wedge-shaped pulmonary infarcts were found in patient 3, and retinitis and subcutaneous lesions developed in patient 4. Patients in septic shock had dysregulated cytokine/chemokine profiles. Patient 4 with relatively milder presentation had increasing levels of interleukin 17 and cytokines in the interferon-γ/interleukin 12 pathway. All survivors required prolonged intravenous antibiotics. Blood cultures grew M. abscessus for all patients, and admission peripheral blood smear revealed AFB for 3 patients. Mycobacterium abscessus was also isolated from respiratory specimens (2 patients), urine (1 patient), and cerebrospinal fluid (1 patient). Time to initial blood culture positivity (patients 1, 2, and 3: ≤52 hours; patient 4: 83 hours) appeared to correlate with disease severity. CONCLUSIONS: Empirical coverage for rapidly growing mycobacteria should be considered in patients with sepsis following cosmetic procedures.

Use of nasopharyngeal aspirate for diagnosis of pneumocystis pneumonia.

Quantitative PCR on nasopharyngeal aspirate (NPA) can achieve high sensitivity and specificity in diagnosing Pneumocystis pneumonia (PCP) compared to microscopic examination of bronchoscopic specimens in a population with low HIV prevalence. Since NPA is a minimally invasive procedure, it is ideal as a screening test for PCP.

Rhinovirus respiratory tract infection in hospitalized adult patients is associated with TH2 response irrespective of asthma.

OBJECTIVES: We assessed the immunological response of hospitalized adult patients with rhinovirus infection, including critically-ill patients. METHODS: The differential white blood cell (WBC) count and the levels of 29 plasma cytokines/chemokines were compared between 50 adult hospitalized patients with rhinovirus infection and 100 age-matched controls with influenza virus infection. RESULTS: The demographics and comorbidities were similar between rhinovirus and influenza patients, but severe disease was more common for the rhinovirus cohort. Rhinovirus patients had significantly higher WBC counts than influenza patients, especially for eosinophil (P = 3.1 × 10-8). The level of the TH2 cytokine IL-5 was significantly higher among rhinovirus patients, while the levels of 9 other cytokines/chemokines were significantly lower among rhinovirus patients. The levels of CXCL-10 (IP-10), CCL-2 (MCP-1), IFN-α2, IFN-γ, IL-10, and IL-15 remained significantly lower among rhinovirus patients after correction for multiple comparisons. Notably, CXCL-10 had the highest area under the receiver operating characteristic curve (AUC) in differentiating rhinovirus from influenza patients (AUC, 0.918). In the patient subgroup without asthma, the difference in the WBC count and cytokine/chemokine levels between rhinovirus and influenza patients remained statistically significant. CONCLUSIONS: Rhinovirus infection was characterized by a prominent TH2 response, even in patients without asthma. CXCL-10 (IP-10) is a potential biomarker in differentiating rhinovirus from influenza infection.

Pulmonary and extrapulmonary complications of human rhinovirus infection in critically ill patients.

BACKGROUND: Human rhinovirus (HRV) is frequently detected in patients with respiratory tract infection. However, the full clinical spectrum of HRV infection in critically ill patients is not well characterized. OBJECTIVE: To evaluate the clinical and virological characteristics of critically ill patients with HRV infection. STUDY DESIGN: HRV-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed on nasopharyngeal aspirate (NPA) specimens from 294 adult patients who required admission into the intensive care unit (ICU). Clinical characteristics were analyzed. HRV genotyping using the 5'UTR-VP4-VP2 region was performed. RESULTS: HRV was detected in NPA specimens of 22 patients (7.5%) by RT-PCR. Dyspnea was the most common presenting symptom (16/22; 72.7%), but seizure also occurred in 5 (22.7%) patients. Exacerbation of underlying disease occurred in 12 (54.5%) patients. Four (18.2%) patients died, and HRV was considered to play a role as the cause of death in 3 patients. Thirteen (59.1%) patients had pneumonia, and the most common radiological finding was consolidation (6/13; 46.2%). Streptococcus pneumoniae was the most common co-pathogen among patients with pneumonia. Among the 9 patients without pneumonia, 3 patients had exacerbation of underlying lung diseases, 3 patients had acute pulmonary edema, 2 patients with diabetes mellitus had acute complications from poor glycemic control, and 1 patient had status epilepticus. HRV-A was the most common species (64.3%), but there was no clear relationship between HRV species and clinical presentation. CONCLUSION: Both pulmonary and extrapulmonary complications of HRV were common in critically ill patients.