Chest CT findings in asymptomatic cases with COVID-19: a systematic review and meta-analysis.

AIM: To determine the overall rate of chest imaging findings in asymptomatic cases, describe the most common patterns found, and determine the rate of later symptom development in these initially asymptomatic cases. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched until 1 May 2020, for studies examining the proportion of positive chest imaging findings in asymptomatic cases diagnosed with COVID-19 and a random-effects meta-analysis of proportions was performed. Heterogeneity was assessed using the I2 statistic. RESULTS: Among 858 non-duplicate studies, seven studies with a total of 231 asymptomatic cases met the inclusion criteria. In the primary analysis, the pooled estimate of the overall rate of positive chest computed tomography (CT) findings among asymptomatic cases was 63% (95% confidence interval [CI]: 44-78%). Among 155/231 cases that were followed up for later symptom development, 90/155 remained asymptomatic and 65/155 developed symptoms during the study period (that ranged between seven and 30 days of follow-up). The pooled estimate of the rate of positive chest CT findings was 62% (95% CI: 38-81%) in cases that remained asymptomatic, while it was 90% (95% CI: 49-99%) in cases that developed symptoms. Among CT findings, the pooled estimate of the overall rate of ground-glass opacities (GGO) at CT alone was 71% (95% CI: 50-86%). Among other CT findings reported, 22/231 patients had GGO with consolidation, 7/231 patients had stripe shadows with or without GGO, and 8/231 patients had GGO with interlobular septal thickening. Among initially asymptomatic cases with positive CT findings, the pooled estimate of the overall rate of later symptom development was 26% (95% CI: 14-43%). CONCLUSION: In COVID-19, asymptomatic cases can have positive chest CT findings, and COVID-19 should be considered among cases with CT abnormalities even when there are no other symptoms. There is a need for close clinical monitoring of asymptomatic cases with radiographic findings as a significant percentage will develop symptoms.

Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta-analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty-three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2­15.8) and 11.9% (95% CI 6.8­18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4­10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0­18.5) for MRSA and 16.2% (95% CI 10.7­22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36­12.90 and RR 10.56; 95% CI 5.58­19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54­17.41 and RR 7.93; 95% CI 2.36­26.67, respectively). Solid organ transplantation is a high-risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

The bacterial signalling molecule indole attenuates the virulence of the fungal pathogen Candida albicans.

AIMS: Indole is a signalling molecule, produced by a number of Gram-positive and Gram-negative bacteria both in nature as well as clinical environments. Here, we explored the effect of bacterial indole and one of its main derivatives on the virulence of the fungal pathogen Candida albicans. METHODS AND RESULTS: We found that indole and its derivate indole-3-acetonitrile (IAN) did not affect the viability of C. albicans. Interestingly, indole and IAN repressed C. albicans biofilm formation as well as the attachment of C. albicans to intestinal epithelial HT-29 cells and inhibited the ability of the yeast to make filaments that are the main virulence factor of C. albicans. In addition, we used the heterologous model host Caenorhabditis elegans to demonstrate in vivo that the presence of indole or IAN attenuates C. albicans infection (P = 0.0188 and P < 0.0001 for indole and IAN, respectively, compared to worms exposed to C. albicans DAY185 alone) and decreases fungal colonization in the nematode gut. Importantly, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that in C. albicans, indole and IAN strongly stimulated the transcription of NRG1. CONCLUSIONS: Indole and IAN attenuates fungal virulence by regulating the transcription of NRG1, a transcriptional factor that influences filamentation and biofilm formation in C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings indicate that the bacterial signalling molecules indole and its derivatives play an inter-kingdom role in dynamic network of microbiota and directly modulate the virulence of fungal C. albicans via NRG1.

Antifungal drug discovery through the study of invertebrate model hosts.

There is an urgent need for new antifungal agents that are both effective and non-toxic in the therapy of systemic mycoses. The model nematode Caenorhabditis elegans has been used both to elucidate evolutionarily conserved components of host-pathogen interactions and to screen large chemical libraries for novel antimicrobial compounds. Here we review the use of C. elegans models in drug discovery and discuss caffeic acid phenethyl ester, a novel antifungal agent identified using an in vivo screening system. C. elegans bioassays allow high-throughput screens of chemical libraries in vivo. This whole-animal system may enable the identification of compounds that modulate immune responses or affect fungal virulence factors that are only expressed during infection. In addition, compounds can be simultaneously screened for antifungal efficacy and toxicity, which may overcome one of the main obstacles in current antimicrobial discovery. A pilot screen for antifungal compounds using this novel C. elegans system identified 15 compounds that prolonged survival of nematodes infected with the medically important human pathogen Candida albicans. One of these compounds, caffeic acid phenethyl ester (CAPE), was an effective antifungal agent in a murine model of systemic candidiasis and had in vitro activity against several fungal species. Interestingly, CAPE is a potent immunomodulator in mammals with several distinct mechanisms of action. The identification of CAPE in a C. elegans screen supports the hypothesis that this model can identify compounds with both antifungal and host immunomodulatory activity.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-α (TNF-α) and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Preclinical and clinical evidence indicate that anti-TNF-α therapy (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-α therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No benefit is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. influenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measles-mumps-rubella) may be contraindicated in people receiving anti-TNF-α therapy, although additional data are needed before definitive recommendations can be made. IMPLICATIONS: Prevention measures should be implemented to reduce the risk of latent tuberculosis or HBV reactivation among individuals receiving anti-TNF-α therapy.

Clostridium difficile--Associated diarrhea: A review.

Clostridium difficile causes 300 000 to 3 000 000 cases of diarrhea and colitis in the United States every year. Antibiotics most frequently associated with the infection are clindamycin, ampicillin, amoxicillin, and cephalosporins, but all antibiotics may predispose patients to C difficile infection. The clinical presentation varies from asymptomatic colonization to mild diarrhea to severe debilitating disease, with high fever, severe abdominal pain, paralytic ileus, colonic dilation (or megacolon), or even perforation. The most sensitive and specific test available for diagnosis of C difficile infection is a tissue culture assay for the cytotoxicity of toxin B. However, this test takes 1 to 3 days to complete and requires tissue culture facilities. Detection of C difficile toxin by means of enzyme-linked immunoassay is more rapid and inexpensive. A minority of patients may require more than 1 stool assay to detect toxin. Oral metronidazole or oral vancomycin hydrochloride for 10 to 14 days are equally effective at resolving clinical symptoms; oral metronidazole is preferred in most cases because of lowered cost and less selective pressure for vancomycin-resistant organisms. Approximately 15% of patients experience relapse after initial therapy and require retreatment, sometimes with an extended, tapering regimen. Immunity appears to be incomplete and predominantly mediated by serum IgG to toxin A. Measures for preventing the spread of the pathogen, appropriate diagnostic testing, and treatment may avert morbidity and mortality due to C difficile-associated diarrhea.

Report of a false-positive HIV test result and the potential use of additional tests in establishing HIV serostatus.

Considering the lifelong implications of a positive human immunodeficiency virus (HIV) test result, physicians should be aware of the limitations of tests for HIV. A 43-year-old man had a reactive enzyme-linked immunosorbent assay and an indeterminate result on Western blot analysis. The results of subsequent enzyme-linked immunosorbent assay and Western blot tests were interpreted as positive, and the patient was informed that he had HIV infection. Persistently undetectable plasma HIV-1 RNA, combined with normal physical examination findings, CD4(+) cell count, and CD4/CD8 ratio, prompted further testing, which revealed that the patient was not infected with HIV. False-positive HIV test results are uncommon, but they can occur. In the appropriate clinical setting, follow-up and the use of other laboratory tests, such as determination of plasma viral load, may help identify such cases.

Risk factors for meticillin-resistant Staphylococcus aureus colonization in dialysis patients: a meta-analysis.

BACKGROUND: Patients on dialysis are particularly vulnerable to meticillin-resistant Staphylococcus aureus (MRSA) infections and MRSA colonization is associated with increased risk for severe infections in this population. AIM: Determination of risk factors for MRSA colonization among dialysis patients. METHODS: This is a systematic review and meta-analysis of studies reporting risk factors of MRSA colonization. We performed a PubMed and EMBASE literature search to identify all studies on risk factors for MRSA colonization among patients undergoing dialysis treatment. Previous hospitalization, type of dialysis access, comorbid conditions, dialysis vintage, gender, length of time on dialysis, and previous antibiotic use were extracted and assessed for possible association with MRSA colonization in this population. FINDINGS: Ten out of 8252 articles, presenting data on 2364 dialysis patients, were included. We found that hospitalization within the previous 12 months [odds ratio (OR): 1.93; 95% confidence interval (CI): 1.04-3.58] and the use of temporary dialysis access (relative risk: 1.66; 95% CI: 1.06-2.60) were associated with a significantly higher risk of MRSA colonization. MRSA carriage was associated with lower serum albumin levels compared to non-carriage (OR: 0.8; 95% CI: 0.68-0.95) and was higher among patients with chronic lung disease (OR: 2.16; 95% CI: 1.04-4.51). There were no data on patients undergoing peritoneal dialysis. CONCLUSION: Active surveillance approaches, including potential decolonization strategies, are suggested to focus on these subgroups of haemodialysis patients with hospitalization within the previous year, temporary dialysis access, lower serum albumin levels, and chronic lung disease comorbidity.

Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature.

We reviewed 776 previously reported and 44 new cases of CNS listeriosis outside of pregnancy and the neonatal period, and evaluated the epidemiologic, diagnostic, and therapeutic characteristics of this infection. Among patients with Listeria meningitis/meningoencephalitis, hematologic malignancy and kidney transplantation were the leading predisposing factors, but 36% of patients had no underlying diseases recognized. The infection occurred throughout life, with a higher incidence before the age of 3 and after the age of 45-50 years. Fever, altered sensorium, and headache were the most common symptoms, but 42% of patients had no meningeal signs on admission. Compared with patients with acute meningitis due to other bacterial pathogens, patients with Listeria infection had a significantly lower incidence of meningeal signs, and the CSF profile was significantly less likely to have a high WBC count or a high protein concentration. Gram stain of CSF was negative in two-thirds of cases of CNS listeriosis. One-third of patients had focal neurologic findings, and approximately one-fourth developed seizures over their course. Mortality was 26% overall, and was higher among patients with seizures and those older than 65 years of age. Relapse occurred in 7% of episodes. Ampicillin for a minimum of 15-21 days (with an aminoglycoside for at least the first 7-10 days) remains the treatment of choice. Cerebritis/abscess due to L. monocytogenes, without meningeal involvement, is less common but may be diagnosed by blood cultures and CNS imaging, or by stereotactic biopsy. Longer antibiotic therapy (at least 5-6 weeks) is needed in the presence of localized CNS involvement.

Central nervous system aspergillosis in patients with human immunodeficiency virus infection. Report of 6 cases and review.

Central nervous system (CNS) aspergillosis is a relatively uncommon complication of human immunodeficiency virus (HIV) infection. We describe 6 patients with the acquired immunodeficiency syndrome (AIDS) who developed CNS aspergillosis, and we review a total of 33 cases of CNS aspergillosis among HIV-infected individuals that were diagnosed by histology and/or culture. All patients were diagnosed with advanced HIV infection. Major risk factors for the disease included neutropenia and corticosteroid use. The most common presenting symptoms were nonspecific neurologic manifestations including headache, cranial or somatic nerve weakness or paresthesia, altered mental status, and seizures. The most common sites of additional Aspergillus involvement were the lungs, sinuses, ears, and orbits, while in one-fourth of the cases CNS was the only site of Aspergillus infection. The final diagnosis of CNS aspergillosis was made on autopsy in more than half the cases, and medical treatment of CNS aspergillosis was unsuccessful in all cases. CNS aspergillosis should be included in the differential diagnosis of HIV-infected patients who present with nonspecific neurologic symptoms and signs. If we take into account the much higher prevalence of invasive aspergillosis of the lungs, the findings in the present report suggest that CNS aspergillosis in HIV-infected individuals occurs more often as a result of direct extension from the sinuses, orbits, and ears than through hematogenous spread from the lungs. Physicians should be aware that the CNS might be the only site of Aspergillus involvement and include CNS aspergillosis in the differential diagnosis of HIV-infected patients presenting with focal neurologic signs and symptoms, especially when the head CT reveals hypodense lesions.

Invasive Aspergillus sinusitis in patients with human immunodeficiency virus infection. Report of 2 cases and review.

Aspergillus sinusitis is an uncommon complication of advanced human immunodeficiency virus (HIV) infection. We describe 2 patients with AIDS who developed histologically proven invasive Aspergillus sinusitis. We also review the findings of 14 histologically documented and 5 probable cases of invasive Aspergillus sinusitis. The literature on the prevalence, predisposing factors, diagnosis, treatment, and prognosis of the infection is reviewed. Major risk factors for the disease are advanced AIDS, chronic sinusitis or otitis, neutropenia, use of corticosteroids and prolonged use of broad spectrum antibiotics. The most common presenting symptoms are nonspecific and include fever, local pain, and swelling. Despite the newer diagnostic and therapeutic approaches discussed herein, the infection is usually fatal in HIV-infected patients. Early diagnosis and aggressive treatment remain the only available means to improve the currently dismal prognosis of Aspergillus sinusitis.

Laboratory testing for infection with the human immunodeficiency virus: established and novel approaches.

The enzyme-linked immunosorbent assay (ELISA) and the Western blot are the primary tests for the diagnosis and confirmation of human immunodeficiency virus (HIV) infection. The ELISA, an inexpensive screening test for antibodies to HIV-1, is both sensitive and specific. The HIV-1 Western blot is a reliable confirmatory test following a repeatedly reactive ELISA. False-positive HIV-1 results with this sequence of tests are extremely rare but can occur, and test results that are inconsistent with clinical or other laboratory information should be questioned, repeated, or supplemented. The US Food and Drug Administration has also approved rapid and more accessible testing methods. Oral mucosal transudate and urine testing are noninvasive testing methods; rapid and home sample collection kits offer easier access to testing.

BK virus in solid organ transplant recipients: an emerging syndrome.

BK virus is a human polyomavirus associated with a range of clinical presentations from asymptomatic viruria with pyuria to ureteral ulceration with ureteral stenosis in renal transplant patients or hemorrhagic cystitis in bone marrow transplant recipients. Infection of renal allografts has been associated with diminished graft function in some individuals. Fortunately, however, the majority of patients with BK virus infections are asymptomatic. The type, duration, and intensity of immunosuppression are major contributors to susceptibility to the activation of BK virus infection. Histopathology is required for the demonstration of renal parenchymal involvement; urine cytology and viral polymerase chain reaction methods are useful adjunctive diagnostic tools. Current, treatment of immunosuppressed patients with polyomavirus viruria is largely supportive and directed toward minimizing immunosuppression. Improved diagnostic tools and antiviral therapies are needed for polyomavirus infections.

Spontaneous bilateral vertebral artery dissections: case report and literature review.

Vertebral artery dissection (VAD) has been increasingly identified as a cause of ischemic stroke in young adults. We report the clinical and radiographic findings in a case of spontaneous bilateral VADs and review the literature on the causes, pathophysiology, diagnostic considerations, and treatment options for VAD. A 29-year-old man was admitted to our hospital after sudden onset of headache and nuchal rigidity that progressed to a posterior lateral medullary syndrome in a 2-week period. The diagnosis of bilateral VADs was based on findings on cranial magnetic resonance imaging and conventional angiography. The patient was given anticoagulant therapy and had no further neurologic deterioration. The differential diagnosis of craniocervical pain in young patients should include arterial dissection of the neck because early diagnosis and treatment may reduce the chances of long-term neurologic sequelae.

Efficacy of deoxycholate amphotericin B and unilamellar liposomal amphotericin B in prophylaxis of experimental Aspergillus fumigatus endocarditis.

OBJECTIVE: To evaluate and compare in vivo the protective efficacy of unilamellar liposomal amphotericin B (L-AmB) with that of deoxycholate amphotericin B (D-AmB) in experimental endocarditis. MATERIAL AND METHODS: In the rabbit model of experimental Aspergillus fumigatus endocarditis, two doses of each antifungal agent (1.5 mg/kg each) were administered intravenously at 4 hours and at 30 minutes before challenge with an inoculum of A. fumigatus. Three days later, the animals were sacrificed, and the aortic vegetations were analyzed. RESULTS: All 19 animals that did not receive chemoprophylaxis acquired endocarditis. In contrast, endocarditis developed in 2 of 10 animals pretreated with D-AmB (P < 0.01) and 3 of 8 animals pretreated with L-AmB (P < 0.01). Both D-AmB and L-AmB prevented the development of endocarditis due to A. fumigatus and decreased the concentration of fungi in the aortic vegetations by more than 1 log10. CONCLUSION: In the rabbit experimental model of Aspergillus endocarditis, D-AmB and L-AmB were equally effective in reducing the incidence of the infection and the tissue burden of fungi.

Pulmonary aspergillosis and invasive disease in AIDS: review of 342 cases.

Aspergillosis is an infrequent but commonly fatal infection among HIV-infected individuals. We review 342 cases of pulmonary Aspergillus infection that have been reported among HIV-infected patients, with a focus on invasive disease. Invasive pulmonary aspergillosis usually occurs among patients with <50 CD4 cells/mm3. Major predisposing conditions include neutropenia and steroid treatment. Fever, cough, and dyspnea are each present in >60% of the cases. BAL is often suggestive, but biopsy specimens are necessary for definite diagnosis. Amphotericin B is the mainstay of treatment and mortality is > 80%. Avoiding neutropenia and judicious use of steroids may be helpful in prevention. Aggressive diagnostic approach, early initiation of treatment, adequate dosing of antifungals, and close follow-up may improve the currently dismal prognosis.

Cellulitis: evaluation of possible predisposing factors in hospitalized patients.

We conducted a prospective study among 62 hospitalized adults, to evaluate the factors that contribute to the development of cellulitis. The majority of patients had multiple possible predisposing factors, and the most common were: diabetes mellitus (31/62), history of cellulitis (30/62), edema (28/62), peripheral vascular disease (25/62), and skin changes suggestive of tinea pedis (20/62). A significant number of patients reported and were clinically noted to have dry skin (42/62). Large controlled studies are needed to evaluate whether aggressive control of possible risk factors can reduce the incidence of cellulitis.

Cutaneous leucocytoclastic vasculitis associated with oxacillin.

A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis.