Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Descriptive analysis of the incidence rate of postacute COVID-19 syndrome in the Republic of Korea Army.

Background: This study aimed to identify the incidence rate of post-coronavirus disease-2019 (COVID-19) conditions in the Republic of Korea (ROK) Army and to investigate the trend of the incidence rate according to changes in dominant variants. Method(s): We used the results of a 19-item, self-completed survey of those who had recovered from COVID-19 in the ROK Army between March 24, 2020, and April 30, 2022. We used both descriptive and multiple logistic regression analyses to identify factors associated with the incidence rate of post-COVID-19 conditions. Result(s): Among the total of 48,623 COVID-19 episodes in the ROK Army, the overall incidence rate of post-COVID-19 conditions was 32.9%. Based on the survey, the incidence of cough was the highest at 15.4%, followed by fatigue (15.1%) and sputum (13.8%). The delta variant had the highest incidence rate of post-COVID-19 conditions at 50.7%, whereas the omicron variant had the lowest at 19.7%. Concerning the type of post-COVID-19 condition, the neuropsychiatric symptoms had the highest incidence at 27.4% when the delta variant was dominant, and the respiratory symptoms were highest at 37.3% when the omicron variant was dominant. In the case of smell and taste symptoms, the incidence rate was high at 21.1% only when the delta variant was predominant. Conclusion(s): The overall incidence rate of post-COVID-19 conditions in the ROK Army was 32.9%. When the delta variant was dominant, the overall incidence as well as the proportion of neuropsychiatric symptoms were high. However, as the omicron variant became dominant, the overall incidence decreased, but the proportion of respiratory symptoms increased.Copyright © Korean Medical Association.

Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023

Descriptive analysis of the incidence rate of postacute COVID-19 syndrome in the Republic of Korea Army

Background: This study aimed to identify the incidence rate of post-coronavirus disease-2019 (COVID-19) conditions in the Republic of Korea (ROK) Army and to investigate the trend of the incidence rate according to changes in dominant variants. Method(s): We used the results of a 19-item, self-completed survey of those who had recovered from COVID-19 in the ROK Army between March 24, 2020, and April 30, 2022. We used both descriptive and multiple logistic regression analyses to identify factors associated with the incidence rate of post-COVID-19 conditions. Result(s): Among the total of 48,623 COVID-19 episodes in the ROK Army, the overall incidence rate of post-COVID-19 conditions was 32.9%. Based on the survey, the incidence of cough was the highest at 15.4%, followed by fatigue (15.1%) and sputum (13.8%). The delta variant had the highest incidence rate of post-COVID-19 conditions at 50.7%, whereas the omicron variant had the lowest at 19.7%. Concerning the type of post-COVID-19 condition, the neuropsychiatric symptoms had the highest incidence at 27.4% when the delta variant was dominant, and the respiratory symptoms were highest at 37.3% when the omicron variant was dominant. In the case of smell and taste symptoms, the incidence rate was high at 21.1% only when the delta variant was predominant. Conclusion(s): The overall incidence rate of post-COVID-19 conditions in the ROK Army was 32.9%. When the delta variant was dominant, the overall incidence as well as the proportion of neuropsychiatric symptoms were high. However, as the omicron variant became dominant, the overall incidence decreased, but the proportion of respiratory symptoms increased.Copyright © Korean Medical Association.

Antibiotic resistance of Klebsiella pneumoniae against the background of the COVID-19 pandemic: experience of the multidisciplinary hospital

Frequency of bacterial co-infections among patients with COVID-19 is not high, and over-prescribing of antibiotics may contribute the selection of resistant strains of enterobacteria and gram-negative non-fermenting bacteria. The aim of the study was to assess the local features of antibiotic resistance of K. pneumoniae and its genetic mechanisms against background of the COVID-19 infection pandemic. Material and methods. There was selected 37 carbapenem-resistant K. pneumoniae strains isolated in 2016, 2017 and 2020 from hospitalized patients, including 15 strains, isolated from patients with COVID-19 infection. Minimal inhibitory concentrations (MICs) of meropenem and colistin were determined by broth microdilution method. Determination of MICs of eravacycline, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam was performed using Sensititre diagnostic system on EUMDROXF plates. Susceptibility to 11 combinations of 2 antibiotics was detected by modified method of multiply combination bactericidal testing. For 4 K. pneumoniae strains high-throughput sequencing was performed, followed with the subsequent search for determinants of antibiotic resistance and virulence, assessment of plasmid profiles. Results. All strains were resistant to meropenem (MIC50 32 mg/l, MIC90 128 mg/l) and produced KPC and OXA-48 carbapenemases. Strains isolated in 2016-2017 were susceptible to colistin (MIC <=2 mg/l), in 2020 only 26.7% of the strains retained their susceptibility (MIC50 64 mg/l, MIC90 256 mg/l). Susceptibility to combinations of two antibiotics with colistin included reduced from 84.6-100% in 2016-2017 till 26.6-66.7% in 2020. The strains isolated in 2020 retained their susceptibility to ceftazidime/avibactam (MIC <=1 mg/l). 5 strains resistant to cefiderocol with a MIC 8 mg/l were identified. Strains 2564 and 3125 isolated in 2020 from sputum of patients with COVID-19 infection belonged to different sequence-types (ST12 and ST23) and contained the blaOXA-48 carbapenemase gene, additionally strain 2564 contained the blaKPC-27carbapenemase gene. Resistance to colistin was caused by inactivation of the mgrB genes due to insertion of IS1 and IS5-like transposons. Conclusion. The performed genetic studies demonstrate a diversity of mechanisms of antibiotic resistance in K. pneumoniae leading to the formation of resistance including to antibiotics that haven't been used in Belarus till now.Copyright © 2021 Geotar Media Publishing Group. All Rights Reserved.

Diagnostic value of sputum nucleic acid amplification testing for COVID-19 a meta-analysis

Objective: To systematically evaluate the diagnostic value of nucleic acid test in sputum for COVID-19 and to determine the suitable population for sputum specimens. Method(s): PubMed, CNKI, Scopus, Web of Science, medRxiv and bioRxiv databases were searched for the diagnostic value of sputum nucleic acid test for COVID-19 from December 2019 to April 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias with QUADAS-2 in the included studies. We used sensitivity, specificity, AUC and DOR to evaluate the diagnostic value of sputum specimens. Result(s): A total of 25 studies were included, including 10,731 subjects. Meta-analysis results showed that: The combined sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), and area under operating characteristic curve (AUC) of sputum nucleic acid for the diagnosis of COVID-19 were 89.2% (95% CI, 86.6-91.4), 97.5% (95% CI, 97.2-97.8), 41.4 (95% CI, 11.7-145.9), 0.9474 (95% CI, 0.8964-0.9846). The results of subgroup analysis showed that the Asian group's DOR was 36.835 (95% CI, 10.83-134.570), and the Non-Asian group's DOR was 66.294 (95% CI, 0.719-6109.09). The DOR was 27.207 (95% CI, 2.860-258.780) in the OPS group and 44.165 (95% CI, 4.828-403.970) in the NPS group. DOR of mild patients was 84.255 (95% CI, 9.975-711.690), the DOR of the severe group was 14.216 (95% CI, 3.527-57.142) and was 19.464 (95% CI, 0.724-522.920) in the cured group. Conclusion(s): Current evidence shows that sputum nucleic acid test is of high diagnostic value for COVID-19. Study area and severity of disease are the influencing factors for the diagnostic accuracy of the sputum nucleic acid test. Due to the limitations on the number and quality of the included studies, the above conclusions need to be verified by more high-quality studies.Copyright © 2023, E-Century Publishing Corporation. All rights reserved.

Analysis on traditional Chinese medicine syndrome characteristics of patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant in a shelter hospital in Shanghai

Objective: To analyze the characteristics of traditional Chinese medicine (TCM) syndromes of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant in a shelter hospital in Shanghai. Methods: A total of 621 patients infected with SARS-CoV-2 omicron variant from Apr. 4 to May 24, 2022 in a shelter hospital in Shanghai were enrolled. The data of the patients, including the general information and common clinical syndromes (such as fever, headache, stuffy nose, runny nose, cough, and sputum), were collected on admission by TCM syndrome electronic scale, and core syndrome characteristics were analyzed base on the proportion of each symptom. The syndromes were divided according to the symptom score of patients, and the differences of disease course among the syndromes were compared. Results: The proportion of patients aged 30 to 49 years old was the highest among 621 patients infected with omicron variant (49.76%, 309/621). The most prominent symptoms were cough and expectoration, accounting for 62.32% (387/621) and 68.12% (423/621), respectively. The more common symptoms included sore throat, stuffy nose, runny nose, fatigue, muscle pain, and headache. White sputum was mostly seen in the expectoration and clear mucus was mostly seen in runny nose. According to the clinical symptoms, the core syndrome characteristic of patients infected with omicron variant was cold epidemic constraint in the lung featuring dampness and toxins. The main syndrome was plague invading the defensive exterior, accounting for 40.10% (249/621). The second and third ones were heat toxin attacking the lung syndrome (29.95%, 186/621) and dampness obstructing (17.55%, 109/621), while the least common syndrome was deficiency of qi and yin (7.73%, 48/621). The course of qi and yin deficiency was longer than the other 3 syndromes (P < 0.05). Conclusion: The core TCM syndrome characteristic of patients infected with SARS-CoV-2 omicron variant is cold epidemic constraint in the lung featuring dampness and toxins. The main syndrome is plague invading the defensive exterior. The pattern tends to convert into qi and yin deficiency along the long course.

Synthesis and evaluation of imidazole-bearing chalcones as a potential treatment for pulmonary aspergillosis

Pulmonary aspergillosis (PA) is a category of respiratory illnesses that significantly impacts the lives of immunocompromised individuals. However, new classifications of secondary infections like influenza associated aspergillosis (IAA) and COVID-19 associated pulmonary aspergillosis (CAPA) only exacerbate matters by expanding the demographic beyond the immunocompromised. Meanwhile anti-fungal resistant strains of Aspergillus are causing current treatments to act less effectively. Symptoms can range from mild (difficulty breathing, and expectoration of blood) to severe (multi organ failure, and neurological disease). Millions are affected yearly, and mortality rates range from 20-90% making it imperative to develop novel medicines to curtail this evolving group of diseases. Chalcones and imidazoles are current antifungal pharmacophores used to treat PA. Chalcones are a group of plant-derived flavonoids that have a variety of pharmacological effects, such as, antibacterial, anticancer, antimicrobial, and anti-inflammatory activities. Imidazoles are another class of drug that possess antibacterial, antiprotozoal, and anthelmintic activities. The increase in antifungal resistant Aspergillus and Candida species make it imperative for us to synthesize novel pharmacophores for therapeutic use. Our objective was to synthesize a chalcone and imidazole into a single pharmacophore and to evaluate its effectiveness against three different fungi from the Aspergillus or Candida species. The chalcones were synthesized via the Claisen-Schmidt aldol condensation of 4-(1H-Imizadol-1-yl) benzaldehyde with various substituted acetophenones using aqueous sodium hydroxide in methanol. The anti-fungal activity of the synthesized chalcones were evaluated via a welldiffusion assay against Aspergillus fumigatus, Aspergillus niger, and Candida albicans. The data obtained suggests that chalcone derivatives with electron-withdrawing substituents are moderately effective against Aspergillus and has the potential for further optimization as a treatment for pulmonary aspergillosis. This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medicine Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the responsibility of the authors and do not necessarily represent the official views of the NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Persistence and prevalence of clinical symptoms in SARS-CoV-2 infected patients

Coronavirus disease 2019 (COVID19) is the recently reported disease caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID19 spreads among population through the close/direct contact and nasal droplets when an infected person sneezes, coughs, talks or breaths. On an average, COVID19 infected patient develops clinical symptoms 5-6 days after the infection and some develops symptoms even after 14 days of infection. Detailed study on the symptoms shown by COVID19 patients can help in identifying individuals so that proper identification and isolation of patients can be done and transmission of virus can be reduced significantly. In this study, a total of 99 (66 males and 33 female) COVID19 infected symptomatic patients without any comorbidities were included. Nasopharyngeal and oropharyngeal swabs were used for the collection of samples from the suspected patients to extract total RNA and perform real time PCR for the detection of genetic material for SARS-CoV-2. Samples with Ct value = 36 in case of Orf1ab gene and E gene with good sigmoidal curve were reported as positive for novel SARS-CoV-2. Fever, shortness of breath, dry cough and cough with sputum production persisted for longer timer and were more common symptoms reported by the COVID19 infected patients. In conclusion, understanding of the clinical symptoms shown by COVID19 infected patients can help in identification and isolation of patients so that transmission of virus can be reduced significantly.

Clinical improvement 2 years after starting elexacaftor/tezacaftor/ivacaftor in patients with advanced lung disease

Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s): This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s): Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s): This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Fungal pneumonia in COVID-19 patients: Risk factors and early prediction

Objective To determine the risk factors for developing secondary fungal pneumonia in moderate to severe coronavirus disease 2019 (COVID-19) cases. Using predictors of fungal infection helps to guide the diagnosis and treatment in these cases and save their lives. Patients and methods A total of 257 patients with moderate to severe COVID-19 pneumonia were examined in this retrospective study at Al Qassimi Hospital of EHS. An assessment of clinical, laboratory, and radiologic findings was performed upon admission. The data were collected and analyzed. Results Overall, 32% of critically ill COVID cases had fungal infection;47% of them were candida, whereas aspergillosis and yeast were positive in 26.5% each. At the time of hospitalization, computed tomography chest findings had a strong correlation with fungal culture results in COVID-19 cases. Fungal infection in COVID-19 cases correlated strongly with metabolic acidosis, high erythrocyte sedimentation rate, high blood sugar, need for mechanical ventilation at admission, vasopressor use, renal replacement, long duration of steroid treatment, long stay in ICU, and long duration on mechanical ventilation. The longer the duration of PCR positivity, the higher the incidence of positive sputum fungal culture result. Conclusion COVID-19-infected patients with other risk factors for fungal infections should always be considered to have fungal infections if pathogenic organisms are isolated from respiratory secretions or other microbiological or immunological markers appear positive. Computed tomography chest finding in COVID-19 cases is an important predictor for fungal infection.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

High Mortality in Hospitalised Virally Suppressed Adults with Hiv in South Africa

Background: Mortality in PWH has been markedly improved by antiretroviral therapy (ART) but there are few reports describing this in the ~5 million virally suppressed (VS) PWH in South Africa(SA). We describe cause of death(CoD) in adults admitted to hospital with suspected pneumonia in SA. Method(s): We enrolled patients from June 2019-October 2021 at four hospitals and then followed them up for >=1 year. Eligibility included: Age >18 years, >=2 signs/symptoms of pneumonia, < 48 hrs since admission. Medical records were reviewed. All had HIV status ascertained and sputum sent for Xpert Ultra and mycobacterial culture. In PWH CD4 count, viral load (VL) and urine lipoarabinomannan were assessed. For those who died, CoD were ed from medical charts and interview of family. We categorised deaths as early: while admitted or to < 30 days after discharge;or late: >=30 days after discharge. We report mortality and CoD in VSPWH (VL<=50 copies/ml), unsuppressed and HIV uninfected(HUI) adults. Result(s): Of 1999 adults, 54% were PWH;61.2% reported receiving ART of whom 43.1% were VS;55.5% were women. Overall median age of VS was 48 years (IQR: 40-55) at entry;34.3% had comorbidities: hypertension (70.1%, obesity 41.3%, diabetes 28.9%) . Only 11.3% were diagnosed with HIV in the past year, 35.0%, had prior TB. Median CD4 count of VS patients was 289 cells/ mm3 (IQR:133-490) and Hb, 12.5g/dL (IQR:10.5-14.0);53.0% had CRP >100mg/ dL and 69.6% had oxygen saturation < 93% on room air;14.8% had >=1 assay positive for TB;and 42.9% were SARS-CoV-2 positive. Overall 25.4% VSPWH died compared to 31.2% and 22.9% of unsuppressed and HUI, respectively;median ages at death were 49 (IQR:43-59), 38 (IQR: 32-47) and 62 (IQR: 53-69) years respectively. Overall median times to early and late death was 8 (IQR: 4-16) and 104 (IQR: 75-254) days, respectively. The leading CoD in VSPWH were: COVID-19 (22.9%), chronic lung disease(CLD) (17.1%),malignancy (12.9%),sepsis, (12.9%) and TB (8.7%);in HIV unsuppressed, CoD were: advanced HIV and opportunistic infections-(TB,PJP)(55.5%), sepsis(9.6%), COVID-19(8.6%);and in HUI: COVID- 19(43.0%), cardiovascular disease (9.0%), TB(9.0%), malignancy (8.5%). Conclusion(s): Mortality in VSPWH admitted with suspected pneumonia was higher than in HUI and occurred 12 years earlier. The challenge for clinicians is to screen for diseases that disproportionately affect VSPWH and to try to prevent recurrent lung infections thereby increasing their comorbidity-free years and reduce mortality gaps.

Towards Tuberculosis control: A Trehalose-based Detection System for live Mycobacterium tuberculosis

Tuberculosis (TB) is second only to COVID-19 as the most lethal cause of death from a single infectious agent. Current primary methods for diagnosing TB infection present significant limitations such as lengthy time-to-result for phenotypic tests, the need for a priori knowledge of Mycobacterium tuberculosis (Mtb) resistance mutations, and prohibitive cost for molecular tests. Here, we present fluorogenic solvatochomic trehalose probes that enables rapid detection of live Mtb. In particular, we designed a 4-N,N-dimethylamino-1,8-naphtha-limide- conjugated trehalose (DMN-Tre) probe that undergoes >700-fold increase in fluorescence intensity when transitioned from aqueous to hydrophobic environments. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. DMN-Tre labeling enabled the rapid, no-wash visualization of mycobacterial and corynebacterial species without nonspecific labeling of Gram-positive or Gram-negative bacteria.DMN-Tre labeling was detected within minutes and was inhibited by heat killing of mycobacteria. Furthermore, DMN-Tre labeling was reduced by treatment with TB drugs, unlike the clinically used auramine stain. Lastly, DMN-Tre labeled Mtb in TB-positive human sputum samples comparably to auramine staining, suggesting that this operationally simple method may be deployable for TB diagnosis.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Efficacy of home respiratory culture kits in people with cystic fibrosis

Background: Respiratory cultures are an important part of clinical care for people with cystic fibrosis (CF). Telemedicine visits during the COVID-19 pandemic have not allowed for routine collection. To address this, the University of Michigan Adult Cystic Fibrosis Program mailed home culture kits to patients. We hypothesized that results from home sputum samples would be consistent with prior cultures obtained in sputum collected in clinic but that self-collected throat swabs would provide false-negative results. We also sought to determine percentage return rate. Method(s): Adults with CF were sent culture kits containing a specimen cup and a throat swab. Patients had the choice to submit either sample for processing. Medical personnel provided written instructions with the culture kits and, on occasion, instructed patients on proper collection techniques via phone. Samples were then refrigerated for up to 24 hours before a delivery service returned the specimen to a University of Michigan laboratory for analysis. Data collected from December 2020 to December 2021 (N = 77) included percentage return rate, result, source, and presence of microorganisms. Pairwise culture data of samples collected in clinic versus home-collected samples within 1 yearwere included in the analysis. Descriptive statistics and Cohen kappa correlation coefficients were computed for all culture data and subgroups (Table 1A-E). Result(s): Of 77 culture kits returned, 46 had corresponding clinic samples collected using the same method, and the remaining 21 were collected using different methods (throat swab vs sputum sample). Overall, approximately 200 kits were mailed to patients, with a return rate of 38.5%. A similar percentage of positive culture results was obtained with same method of collection: sputum and throat samples (Table 1C, D, E), although the discordance rate between cultures collected in clinic and at home ranged from approximately 10% to 30%. Correlation between clinic and home culture data was generally good throughout, except for clinic Table 1 ( 115): Analysis of respiratory culture results for (A) all cultures, (B) different collection, and (C, D, E) same collection method. *p < 0.05. Cohen kappa correlation coefficient between groups: poor agreement <0.20;fair agreement = 0.21-0.40;moderate agreement = 0.41-0.60;good agreement = 0.61-0.80;very good agreement = 0.81-1.00. PsA = Pseudomonas aeruginosa;Staph = Staphylococcus aureus.(Table Presented)versus home throat swabs, probably because of a lowevent rate in the small sample size. Conclusion(s): The data suggest that, overall, clinic and home culture kits provide similar positive results, although discordance in specific culture results was common. This may be due to natural fluctuations from culture to culture in people with CF. A limitation of this study is that the cultures being compared in our study were not completed on the same day. Nevertheless, our data also indicate that collection technique may influence results for certain microorganisms. How these differences might influence antibiotic selection and treatment outcomes in the era of telemedicine requires more investigation. The return rate was found to be relatively low, demonstrating the need for interventions to improve patient outreach and compliance.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Viral shedding time and its influencing factors in different site samples of patients infected with Severe acute respiratory syndrome coronavirus 2 omicron BA.2 variant

Objective: To analyze the viral shedding time and its influencing factors in different site samples of patients infected with severe acute respiratory syndrome coronavirus 2 (SARA-CoV-2) omicron BA.2 variant. Methods: Real-time fluorescence polymerase chain reaction was used to detect SARS-CoV-2 nucleic acid in nasopharyngeal swab, sputum and anal swab from 217 patients with coronavirus disease 2019 (COVID-19) who were infected with severe acute respiratory syndrome coronavirus 2 omicron BA.2 variant confirmed by gene sequencing in The First Affiliated Hospital of Naval Medical University (Second Military Medical University). The differences of viral shedding time of different site samples were compared. Stratified analysis and multiple linear regression analysis were used to explore the influencing factors of viral shedding time in different site samples. Results: The age of the 217 COVID-19 patients was 32.0 (24.0, 50.5) years old, 59.0% of them were males (n=128), and 41.0% were females (n=89). Eight (3.7%) cases were diagnosed with asymptomatic infection, 184 (84.8%) cases were mild type, 21 (9.7%) cases were moderate type, 3 (1.4%) cases were severe type, and 1 (0.5%) case was critical type. A total of 70 (32.3%) patients were treated with molnupiravir. The viral shedding time of SARS-CoV-2 nucleic acid in nasopharyngeal swab, sputum and anal swab was 13.0 (11.0, 17.0) d, 16.5 (13.0, 21.0) d and 10.0 (5.3, 11.0) d, respectively, with the differences being significant between them (all P<0.001). Age 60 years old, underlying diseases (especially hypertension, coronary artery diseases, or neurological diseases), and clinical classification of moderate type were risk factors for prolonged viral shedding time in nasopharyngeal swab;male sex and underlying diseases were risk factors for prolonged viral shedding time in sputum;and male sex was a risk factor for prolonged viral shedding time in anal swab. Multiple linear regression analysis showed that critical type was an independent risk factor for prolonged viral shedding time in nasopharyngeal swab (P<0.05), and male sex and underlying diseases were independent risk factors for prolonged viral shedding time in sputum (both P<0.05). Conclusion: Among patients infected with omicron BA.2 variant, the viral shedding time in sputum is the longest and that in anal swab is the shortest. Male patients and/or patients with underlying diseases have longer viral shedding time in sputum.

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Co-infections and antimicrobial use in hospitalized patients with moderate-severe COVID-19

Introduction/Aim: Coinfection in COVID-19 has been reported internationally, however, data on prevalence and outcomes in Australia is lacking. This study aimed to determine the prevalence and microbiology of coinfections, associated antimicrobial use, and outcomes in hospitalised patients with moderate-severe COVID-19 admitted to the Sunshine Coast University Hospital (SCUH). Method(s): A retrospective observational cohort study of adult patients admitted to the SCUH from February to July 2022 with moderate-severe COVID-19 was conducted. Demographics, comorbidities, laboratory, microbiological and radiological results, antimicrobial use, and hospital length of stay were collected. All-cause 30-day mortality and ICU admission were also collected, and incidence rate ratios (IRR) were calculated. Result(s): Sixty-six patients (57% male;median age 78.3) were captured. 13 coinfections occurred in 11 (16.7%) patients. Microbiological testing was performed in 94% of patients;respiratory viral PCR in 78.8%, blood cultures in 69.7%, sputum cultures in 25.8%, urinary antigens in 13.6% and atypical serology in 12.1%. Bacterial pathogens were most prevalent (53.8% of coinfections), whilst viral and fungal infections accounted for 30.8% and 15.4%, respectively. The most common pathogens were Streptococcus pneumoniae, Pseudomonas aeruginosa and influenza A. Most patients (74.2%) received empirical antibiotic therapy (mean = 5.5 days), with similar rates of use between those with coinfection (66.7%) and those without (75.9%). Overall patient mortality was 10.6%, with coinfections demonstrating a higher 30-day mortality (IRR = 2.0). Coinfected patients were seven times more likely to experience ICU admission (IRR = 7.5) compared to patients without coinfections. Conclusion(s): The prevalence of confirmed coinfection in hospitalised patients with moderate-severe COVID 19 was low;however, antimicrobial use was high. Importantly, patients with coinfections were twice as likely to die, and seven times more likely to be admitted to ICU. This study indicates the importance of developing improved diagnostic tools to identify coinfection and to help guide appropriate antimicrobial use.

Respiratory microbiological surveillance in people with cystic fibrosis-analysis of respiratory samples before and after elexacaftor/tezacaftor/ivacaftor in a large adult U.K. cystic fibrosis center

Background: Pathogen surveillance is crucial but has become more challenging in the era of highly effective modulator therapy (HEMT), with many people with cystic fibrosis (PwCF) noting a considerable reduction or even absence of sputum on elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). This challenge has been exacerbated by reduced face-toface contact with patients because of variable COVID-19 government restrictions on travel and social interaction (lockdowns) since March 20, relying on PwCF returning high-quality samples by mail. For those with pre-established bronchiectasis, it is likely that chronic infections and risk of new acquisition of infections remain on ELX/TEZ/IVA, although registry data suggest less prevalence of respiratory microorganisms on IVA [1]. We aimed to examine the impact of ELX/TEZ/IVA on frequency of respiratory pathogen surveillance and microorganism growth in our large, adult CF center. Method(s): A retrospective analysis of pathology results from respiratory samples received from March 19 to December 21, 2020, was completed for all patients commenced on ELX/TEZ/IVA at our CF center. Result(s): Respiratory samples from 216 PwCF who had commenced ELX/ TEZ/IVAwere analyzed. Median start date of ELX/TEZ/IVAwas October 10,2020. Before ELX/TEZ/IVA, the average number of respiratory samples per month was 108. This declined by 55% to an average of 48 per month when the first 50 PwCF commenced on ELX/TEZ/IVA and to 20 per month (82% reduction from pre-ELX/TEZ/IVA) when 100 PwCF had commenced ELX/ TEZ/IVA. The number of positive samples per month decreased from January 20, 2020, correlating with the introduction of ELX/TEZ/IVA and the reduction of respiratory samples received (Figure 1). The proportion of cough swabs and sputum samples remained similar from March 19 to December 21, 2020. (Six-month average showed that 19% of samples were cough swabs and 80% sputum for March to June 2019 and July to December 2021). We found no significant changes in proportion of samples positive for non-Pseudomonas spp. gram-negative organisms, Burkholderia spp., or gram-positive organisms (predominantly S. aureus) isolated over the period. There was a reduction by more than 50% of fungi and Candida spp. and a slight trend toward an increase in Pseudomonas spp. (mainly P. aeruginosa). Forty percent of PwCF who had one respiratory sample after ELX/TEZ/IVA initiation and 20% of those who had two or more samples showed a change in organism growth after ELX/TEZ/IVA initiation. In nearly 50% of these cases, the organism changed from gram negative to gram positive (P. aeruginosa to S. aureus in 69% of cases).(Figure Presented) Figure 1. Number of positive respiratory samples per month and number of people with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor March 19 to December 21, 2020 Conclusion(s): The introduction of ELX/TEZ/IVA and its impact on sputum production has reduced surveillance of our patients' respiratory microbiology. This has been exacerbated by reduced face-to-face contact with patients due to the COVID-19 pandemic. The trends showa reduction in the isolation of fungi and yeasts and a slight increase in isolating Pseudomonas spp. In those who we have seen a change in organism growth, many have gone from gram-negative to gram-positive organisms. These data highlight the challenges of monitoring for new positive cultures and changes in microbiology cultures in the era of HEMT.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Comparable detection of nasopharyngeal swabs and induced sputum specimens for viral nucleic acid detection of suspected novel coronavirus (SARS-Cov-2) patients in Fayoum governorate, Egypt.

Background: The most commonly utilized samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) are nasopharyngeal swabs (NPS) and oropharyngeal swabs. However, there are some drawbacks. For SARS-CoV-2 detection, induced sputum might be analyzed and may be equivalent to pharyngeal swabs. This study was done to assess the potential superiority of induced sputum over NPS for SARS-CoV-2 detection. Sixty symptomatic COVID-19 patients who attended Fayoum University Hospitals in Fayoum Governorate, Egypt, were included in this cross-sectional descriptive study. Paired NPS and induced sputum samples were collected from each subject on the third and tenth days after symptoms began for RT-qPCR SARS-COV2 diagnosis. Results: At day 3, 52 (86.7%) of NPS and 48 (80.00%) of induced sputum specimens had positive RT-qPCR results with a significant statistical difference (P = 0.001). At day 10, 41 induced sputum samples (68.3%) were negative, while 19 (31.7%) were positive. Only three (5.0%) of the 19 positive induced sputum samples tested positive for NPS. NPS samples had a higher viral load than induced sputum samples at day 3 [25 (41.7%) vs. 23 (38.3%)]. At day 10, induced sputum samples had a higher viral load than NPS [9 (15.0%) vs. 6 (10.0%)]. A statistically significant positive correlation between the viral load value of the NPS and the induced sputum sample at day 3 (r = 0.497, p = 0.00) denoting similarity in the results of the two types of samples. By ROC analysis, the highest area under the curve for the overall CT value of the induced sputum was (0.604), with a statistically significant difference (p value = 0.0418). Conclusion: In the early stages of the disease, induced sputum and NPS tests had comparable results, but NPS yielded more false negative results later in the disease course than an induced sputum sample, which yielded higher sample positivity and viral load than NPS. Furthermore, induced sputum collection is a straightforward, non-invasive, and risk-free method. As a result, induced sputum could be useful for COVID-19 confirmation in patients with radiologically or epidemiologically suspected COVID-19 who have a negative NPS or in difficult-to-diagnose COVID-19 patients.

Microbiological monitoring of COVID-19 patients in the ICU: a prospective observational study.

Objective. To study spectrum of pathogens and the time to colonization of respiratory samples in patients with severe and critical COVID-19 as well as to analyze incidence of nosocomial infections and structure of prescribed antibacterial drugs. Materials and methods. The prospective observational study included patients aged 18 years and older with confirmed severe and critical COVID-19 from December 2021 to February 2022. During the first 48 hours and then every 2-3 days of hospitalization, a respiratory sample was collected: sputum, tracheal aspirate (if intubated), bronchoalveolar lavage (if bronchoscopy was performed) for microscopy and microbiological examination. Some patients were screened for invasive aspergillosis. Clinical and demographic data, comorbidities, pathogenetic therapy for COVID-19, antibiotic therapy, cases of probable/documented bacterial nosocomial infections, antibiotic-associated diarrhea, and hospital treatment outcomes were recorded. Results. A total of 82 patients were included in this study. Patients with lung parenchyma involvement of more than 50% by computer tomography predominated;most of them (77%) required intubation and mechanical ventilation due to progression of respiratory failure, and 76% of patients had a lethal outcome. During the first 48 hours, a respiratory sample was obtained from 47 patients;the rest of the patients presented with non-productive cough. No growth of microorganisms was detected in 31 (36.8%) cases;clinically significant pathogens were detected in 16 (19.5%) patients. A subsequent analysis included data from 63 patients with a sufficient number of samples for dynamic observation were used. During the first 3 days of ICU stay, the most common bacterial pathogens were Klebsiella pneumoniae without acquired antibiotic resistance and methicillin-susceptible Staphylococcus aureus. From 3rd day and afterwards, an increase in the proportion of Acinetobacter baumannii, other non-fermenting bacteria, and carbapenem-resistant Enterobacterales was noted. Among the pathogens causing lower respiratory tract infections, A. baumannii and carbapenem-resistant K. pneumoniae were predominant pathogens and accounted for 76% of cases. Positive galactomannan test results were obtained in 4 cases. Conclusions. The study confirmed importance of bacterial nosocomial infections in patients with severe and critical COVID-19. In the case of the development of nosocomial lower respiratory tract infections, empirical antimicrobial therapy should take into account the predominance of carbapenem-resistant Enterobacteria and A. baumannii, as well as the possibility of invasive aspergillosis.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.