Infections In Clinical Practice Research Articles

Prevention and Risk Assessment of Cardiac Device Infections in Clinical Practice.

The implantation of cardiac electronic devices (CIEDs), including pacemakers and defibrillators, has become increasingly prevalent in recent years and has been accompanied by a significant rise in cardiac device infections (CDIs), which pose a substantial clinical and economic burden. CDIs are associated with hospitalizations and prolonged antibiotic therapy and often necessitate device removal, leading to increased morbidity, mortality, and healthcare costs worldwide. Approximately 1-2% of CIED implants are associated with infections, making this a critical issue to address. In this contemporary review, we discuss the burden of CDIs with their risk factors, healthcare costs, prevention strategies, and clinical management.

CLINICAL AND PHARMACOLOGICAL ASPECTS OF APPLYING GLUCOCORTICOSTEROIDS FOR SARS-COVID-2 INFECTION: REVIEW ARTICLE

In recent years, the SARS-CoV-2 pandemic has become one of the unexpected and very serious challenges for public health around the world. Moreover, SARS-CoV-2 infection led to the development of acute respiratory distress syndrome as a result of excessive systemic inflammation, and the development of multiple organ failure, and later death. Moreover, the problem of eliminating excessive systemic inflammation, that is, reducing the production of pro-inflammatory cytokines in SARS-CoV-2, remains open. In this regard, the use of glucocorticosteroids for infection caused by SARS-CoV-2 remains quite controversial. The basis for the routine use of steroids in intensive care protocols for SARS-CoV-2 is clearly insufficient and remains the subject of further research. This review provides an analysis of literary sources, guidelines, and modern international recommendations on pathogenetic therapy of SARS-CoV-2 to prevent and eliminate hyperproduction of pro-inflammatory cytokines using glucocorticosteroid agents. The purpose of the work is to conduct an analysis of modern literary sources regarding the modern features of the clinical and pharmacological justification of the use of glucocorticosteroids in SARS-CoV-2 infection in clinical practice. The analysis of the scientific literature demonstrates that today glucocorticosteroid therapy cannot be recommended for routine use in therapeutic practice in patients with SARS-CoV-2 infection. Thus, with a mild course of SARS-CoV-2 infection, when the patient does not need oxygen support, GCS therapy is contraindicated. With a severe course of SARS-CoV-2, when the patient develops acute respiratory distress syndrome with severe respiratory failure, when there is a need for oxygen therapy, mechanical ventilation or ECMO, the use of corticosteroids is extremely necessary, and may be recommended for mandatory use. There is a pressing need for a comprehensive definition of the optimal glucocorticosteroid agent, indications, dosage, and duration of use in SARS-CoV-2 infection therapy programs. This should be done while considering biomarkers of the severity of the inflammatory process and biomarkers of the body's response to glucocorticosteroid agents.

The small RNA PrrH aggravates Pseudomonas aeruginosa-induced acute lung injury by regulating the type III secretion system activator ExsA.

Pseudomonas aeruginosa is a Gram-negative bacterium and the leading cause of nosocomial pneumonia. The pathogenicity of P. aeruginosa is due to the secretion of many virulence factors. Small regulatory RNAs (sRNAs) regulate various bacterial adaptations, especially virulence. Therefore, understanding the mechanism by which sRNAs regulate virulence is necessary for understanding the pathogenicity of P. aeruginosa and the treatment of the related disease. In this study, we demonstrated that PrrH enhances the pathogenicity of P. aeruginosa by binding to the coding sequence regions of the ExsA, the master regulatory protein of type III secretion system, causing severe lung injury and exacerbating the inflammatory response and apoptosis. These findings revealed that PrrH is a crucial molecule that positively regulates ExsA. Type III-positive strains are often associated with a high mortality rate in P. aeruginosa infections in clinical practice. Therefore, this discovery may provide a new target for treating P. aeruginosa infections, especially type III-positive strains.

Sub-minimum inhibitory concentrations (sub-MICs) of colistin on Acinetobacter baumannii biofilm formation potency, adherence, and invasion to epithelial host cells: an experimental study in an Iranian children's referral hospital.

Here, we described the efficacy of colistin sub-minimum inhibitory concentrations (sub-MICs) on biofilm-forming activity, host epithelial cell adherence, and invasion capacity of Acinetobacter baumannii strains collected from children admitted to the Children's Medical Center Hospital. Biofilm formation potency of A. baumannii clinical isolates was measured using a 96-well microtiter plate assay. Distribution of biofilm-related genes, including bap, abaI, ompA, csuE, and blaPER-1, was detected by PCR. The mRNA expression level of ompA and csuE was measured by qPCR in the presence of ¼ and ½ MICs of colistin. A. baumannii adhesion and invasion to eukaryotic host cells were phenotypically assayed at sub-MICs of colistin. Eighty percent (56/70) and 35.7% (25/70) of A. baumannii isolates were multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes, respectively. The strong, moderate, and weak biofilm producers of A. baumannii were 37.1% (26/70), 32.8%, (23/70), and 22.8% (16/70), respectively. The frequencies of biofilm-associated genes were 100% for abaI, ompA, and csuE, followed by 22.8% (16/70) and 24.3% (17/70) for bap and blaPER-1, respectively. The downregulation of csuE and ompA expression levels was observed in the sub-MIC of colistin. In vitro cell culture study showed a decreased capability of A. baumannii to adhere to the human epithelial cells at sub-inhibitory doses of colistin; however, none of the isolates could invade HEp-2 cells. Our study showed that the genes encoding biofilm-associated proteins undergo downregulation in expression levels after exposure to sub-MICs of colistin in A. baumannii. Longitudinal in vivo studies are needed to fully understand the clinical aspects of pathogenicity mechanisms and evolutionary dynamics of drug resistance.IMPORTANCESince the toxicity of colistin is dose dependent, there is a focus on strategies that reduce the dose while maintaining the therapeutic effect of the drug. Our findings about sub-inhibitory doses of colistin provide a novel insight into the logical use of colistin to treat and control Acinetobacter baumannii-related infections in clinical practice.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Determination of the Diagnostic Performance of Laboratory Tests in the Absence of a Perfect Reference Standard: The Case of SARS-CoV-2 Tests.

Currently, assessing the diagnostic performance of new laboratory tests assumes a perfect reference standard, which is rarely the case. Wrong classifications of the true disease status will inevitably lead to biased estimates of sensitivity and specificity. Using Bayesian' latent class models (BLCMs), an approach that does not assume a perfect reference standard, we re-analyzed data of a large prospective observational study assessing the diagnostic accuracy of an antigen test for the diagnosis of SARS-CoV-2 infection in clinical practice. A cohort of consecutive patients presenting to a COVID-19 testing facility affiliated with a Swiss University Hospital were recruited (n = 1465). Two real-time PCR tests were conducted in parallel with the Roche/SD Biosensor rapid antigen test on nasopharyngeal swabs. A two-test (PCR and antigen test), three-population BLCM was fitted to the frequencies of paired test results. Based on the BLCM, the sensitivities of the RT-PCR and the Roche/SD Biosensor rapid antigen test were 98.5% [95% CRI 94.8;100] and 82.7% [95% CRI 66.8;100]. The specificities were 97.7% [96.1;99.7] and 99.9% [95% CRI 99.6;100]. Applying the BLCM, the diagnostic accuracy of RT-PCR was high but not perfect. In contrast to previous results, the sensitivity of the antigen test was higher. Our results suggest that BLCMs are valuable tools for investigating the diagnostic performance of laboratory tests in the absence of perfect reference standard.

Application of artificial intelligence in endoscopic image analysis for the diagnosis of a gastric cancer pathogen-Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is the principal cause of chronic gastritis, gastric ulcers, duodenal ulcers, and gastric cancer. In clinical practice, diagnosis of H. pylori infection by a gastroenterologists’ impression of endoscopic images is inaccurate and cannot be used for the management of gastrointestinal diseases. The aim of this study was to develop an artificial intelligence classification system for the diagnosis of H. pylori infection by pre-processing endoscopic images and machine learning methods. Endoscopic images of the gastric body and antrum from 302 patients receiving endoscopy with confirmation of H. pylori status by a rapid urease test at An Nan Hospital were obtained for the derivation and validation of an artificial intelligence classification system. The H. pylori status was interpreted as positive or negative by Convolutional Neural Network (CNN) and Concurrent Spatial and Channel Squeeze and Excitation (scSE) network, combined with different classification models for deep learning of gastric images. The comprehensive assessment for H. pylori status by scSE-CatBoost classification models for both body and antrum images from same patients achieved an accuracy of 0.90, sensitivity of 1.00, specificity of 0.81, positive predictive value of 0.82, negative predicted value of 1.00, and area under the curve of 0.88. The data suggest that an artificial intelligence classification model using scSE-CatBoost deep learning for gastric endoscopic images can distinguish H. pylori status with good performance and is useful for the survey or diagnosis of H. pylori infection in clinical practice.

Barnacle-Inspired Wet Tissue Adhesive Hydrogels with Inherent Antibacterial Properties for Infected Wound Treatment.

Currently, antibiotics are the most common treatment for bacterial infections in clinical practice. However, with the abuse of antibiotics and the emergence of drug-resistant bacteria, the use of antibiotics has faced an unprecedented challenge. It is imminent to develop nonantibiotic antimicrobial agents. Based on the cation-π structure of barnacle cement protein, a polyphosphazene-based polymer poly[(N,N-dimethylethylenediamine)-g-(N,N,N,N-dimethylaminoethyl p-ammonium bromide (ammonium bromide)-g-(N,N,N,N-dimethylaminoethyl acetate ethylammonium bromide)] (PZBA) with potential adhesion and inherent antibacterial properties was synthesized, and a series of injectable antibacterial adhesive hydrogels (PZBA-PVA) were prepared by cross-linking with poly(vinyl alcohol) (PVA). PZBA-PVA hydrogels showed good biocompatibility, and the antibacterial rate of the best-performed hydrogel reached 99.81 ± 0.04% and 98.80 ± 2.16% against Staphylococcus aureus and Escherichia coli within 0.5 h in vitro, respectively. In the infected wound model, the healing rate of the PZBA-PVA-treated group was significantly higher than that of the Tegaderm film group due to the fact that the hydrogel suppressed inflammatory responses and modulated the infiltration of immune cells. Moreover, the wound healing mechanism of the PZBA-PVA hydrogel was further evaluated by real-time polymerase chain reaction and total RNA sequencing. The results indicated that the process of hemostasis and tissue development was prompted and the inflammatory and immune responses were suppressed to accelerate wound healing. Overall, the PZBA-PVA hydrogel is shown to have the potential for infected wound healing application.

The Appropriateness of Empirical Antimicrobial Treatment of Uncomplicated Urinary Tract Infection in Adult Female Patients in Jazan Region, Saudi Arabia.

Uncomplicated urinary tract infection (uUTI) is one of the most prevalent bacterial infections in clinical practice. Empirical treatment is used commonly; thus, knowledge of the local antimicrobial susceptibility pattern is crucial to avoid the growing antibiotic resistance. The aim of this study is to evaluate the effectiveness of the empirical treatment of uUTI and determine the susceptibility pattern for common uUTI causative microorganisms at outpatient clinics in hospitals in the Jazan region. This is a prospective observational study of 120 patients with uncomplicated urinary tract infections attending internal medicine outpatient clinics in Al-Hayat Jazan hospital, Saudi Arabia, from September 2021 to January 2023. In total, 120 patients were included in the study. The mean age of the participants was 48.53 ± 9.29. Risk factors for UTI were found in 57.5%, and type 2 diabetes mellitus (DM) was the major risk factor (27.5%). The most common causative microorganism was Escherichia coli (E. coli) (87.5%), followed by Klebsiella pneumoniae (5%), Staphylococcus aureus, Enterobacter spp., and Enterococcus spp. (2.5%). Nitrofurantoin was the most effective antimicrobial agent (sensitivity rate of 91.7%) against all microorganisms, followed by Ciprofloxacin (75%). This study concluded that nitrofurantoin and Ciprofloxacin are suitable empirical treatments for uncomplicated urinary tract infection in the Jazan region, and increased resistance against trimethoprim/sulphamethoxazole (TMPSMX) and cefaclor was observed; thus, empirical therapy with these agents should be reconsidered in local guidelines. Wide surveillance research is necessary to monitor effective empirical therapies and to evaluate the regional antimicrobial susceptibility pattern.

Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis

BackgroundMultidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. MethodsPubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. ResultsMeta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. ConclusionsThis study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.

Antibacterial Effect of Raw Honey on Clinical Bacterial Isolates of Pseudomonas aeruginosa, Staphylococcus aureus, And Escherichia coli

The development of multiple drug resistant bacteria, causing human infection in clinical practice unfold the use of natural sources like honey, medicinal plants of non-antibiotic drugs, having antibacterial potentiality. Beside the medicinal plants, the antibacterial effects of raw honey on clinical bacterial isolates of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli were studied. The raw honey samples were collected from the beekeepers at Umugwu Ezedike in Udi Local Government Area Enugu State Nigeria. The honey samples were prepared by diluting the honey with distilled water to produce honey of various concentrations, i.e. 20% v/v, 40% v/v, 60% v/v, 80% v/v and 100% v/v. The clinical isolates from Accident and Emergency Department University of Nigeria Teaching Hospital Ituku-Ozalla Enugu were cultured in Nutrient agar, Cetrimide agar, Macconkey agar, and Methylene Blue agar (EMB) for identification and confirmation. The antibacterial effects of raw honey on the clinical bacterial isolates were evaluated in-vitro using agar well diffusion methods with Gentamicin as control. The results showed that raw honey demonstrated antibacterial effect against the test isolates with higher effect in Staphylococcus aureus (with zone of inhibition of 21mm) followed by Pseudomonas aeruginosa (19mm) and Escherichia coli (18mm). The minimum inhibitory concentration (MIC) of the extract from this study ranges from 12.5-50mg/ml while the minimum bactericidal concentration (MBC) of the extracts ranges from 25-50mg/ ml. Hence, raw honey has antibacterial properties and can also serve as a therapeutic substance for the treatment of bed sores, and other infections resulting from burns.

Terapeutic Remission of Community Acquired Pneumonia Caused by Rothia Mucilaginosa in an Adult Patient with Idiopathic Pulmonar Fibrosis

Rothia Mucilaginosa (RM) is part of the microbiota of the pharynx and upper respiratory tract. RM is a gram-positive, enveloped, coagulase-negative coccus of the family Micrococcaceae. Clinical manifestations range from mild bronchitis to recurrent pneumonia and lung abscess. It is difficult to determine the clinical significance of this organism in respiratory specimens, therefore, in the diagnosis of pneumonia caused by R. mucilaginosa, bronchoscopy specimens should be cultured. Risk factors associated with Rothia are hematologic malignancies and neutropenia. At present, the importance of Rothia in various pathologies remains unclear due to its difficulty in culture and high potential for contamination at the time of sampling. Although it is an oral microbiota, it has been implicated in pneumonia after being identified in sputum or bronchoalveolar lavage smears and in infectious lesions of the respiratory tract, such as lung abscess and empyema. The challenge of MRI infection in clinical practice is deciding whether it is a real infection or a product of sample contamination. We present the case of a 50-year-old adult patient, without neutropenia, without hematological malignancy, with progressive idiopathic pulmonary fibrosis (IPF) of 1 year of evolution. On admission to the hospital, this person presented signs of respiratory failure, tachycardia, upper rales. auscultation and 85% oxygen saturation, that's why he went through many different studies to diagnose Rothia Mucilaginosa pneumonia.

Effectiveness and tolerability of dolutegravir/lamivudine for the treatment of HIV-1 infection in clinical practice.

To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018-2021. We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) <50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (n = 949, 43.9%), DTG + FTC/tenofovir disoproxil fumarate (TDF) (n = 282, 13.1%), DTG/3TC/abacavir (ABC) (n = 255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (n = 147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (n = 126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30-0.74) compared with dolutegravir/lamivudine.For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.

Reasons for requesting an interferon gamma release test from internal medicine and rheumatology clinics and evaluation of the results

Background/Aim: Tuberculosis is a disease involving many systems, such as the lung, gastrointestinal system, genitourinary system, etc. Detecting this disease in its latency significantly reduces the morbidity and mortality associated with tuberculosis. One of the tests used in latent TB screening is the interferon gamma release test. In rheumatology practices, it is routinely used to screen for latent tuberculosis infections before treatment with biological agents and Janus kinase (JAK) inhibitors, and it can also be used to exclude tuberculosis infection in clinical practice. In our study, we aimed to evaluate the reasons for requesting interferon gamma release tests and the results of this test in patients who requested it. Methods: Patients admitted to internal medicine and rheumatology outpatient clinics were retrospectively screened within the retrospective cohort study. In total, 364 patients who requested interferon gamma release testing were included in the study. Nine patients with unclear test results were excluded. Laboratory results, demographic data, reasons for requesting the interferon gamma release test, and results were evaluated. Results: The interferon gamma release test was requested by 355 patients. Of these, 266 patients (74.9%) asked for latent tuberculosis screening before treatment with biological agents and JAK inhibitors. This was followed by patients with peripheral lymphadenopathy-lung nodules, patients with unexplained elevated acute phase reactants, and patients with constitutional symptoms, respectively. Ten out of 107 patients (9.3%) had an active tuberculosis infection, while six out of ten patients (60%) had pulmonary tuberculosis, and four (40%) had extrapulmonary tuberculosis. Conclusion: The most common reason for requesting the interferon gamma release test in internal medicine and rheumatology clinics was screening for latent tuberculosis before treatment with biologic agents and JAK inhibitors. In internal medicine, it has been observed that this test can also be requested by patients with constitutional symptoms, unexplained elevated acute phase reactants, and a preliminary diagnosis of tuberculosis in order to rule out or strengthen the preliminary diagnosis.

Colistin Resistance Genes in Broiler Chickens in Tunisia.

Colistin is a polymyxin antibiotic that has been used in veterinary medicine for decades, as a treatment for enterobacterial digestive infections as well as a prophylactic treatment and growth promoter in livestock animals, leading to the emergence and spread of colistin-resistant Gram-negative bacteria and to a great public health concern, considering that colistin is one of the last-resort antibiotics against multidrug-resistant deadly infections in clinical practice. Previous studies performed on livestock animals in Tunisia using culture-dependent methods highlighted the presence of colistin-resistant Gram-negative bacteria. In the present survey, DNA extracted from cloacal swabs from 195 broiler chickens from six farms in Tunisia was tested via molecular methods for the ten mobilized colistin resistance (mcr) genes known so far. Of the 195 animals tested, 81 (41.5%) were mcr-1 positive. All the farms tested were positive, with a prevalence ranging from 13% to 93%. These results confirm the spread of colistin resistance in livestock animals in Tunisia and suggest that the investigation of antibiotic resistance genes by culture-independent methods could be a useful means of conducting epidemiological studies on the spread of antimicrobial resistance.

Development of serological assays to identify Helicobacter suis and H. pylori infections.

Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H.suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H.suis urease activity often yield negative results, and there is no reliable method for diagnosing H.suis infection in clinical practice without gastric biopsy specimens. This study presents the world's first use of whole-bacterial cell ELISA to simultaneously assess H.suis and H.pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H.suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H.pylori test.

Population pharmacokinetics of levornidazole in healthy subjects and patients and sequential dosing regimen proposal using pharmacokinetic/pharmacodynamic analysis.

Although levornidazole sequential treatment has been used for anaerobic infection in clinical practice, there is no evidence-based dosing regimen. This study aimed to evaluate the pharmacokinetics (PK) of levornidazole in healthy subjects and patients and to propose an evidence-based sequential dosing regimen by pharmacokinetic/pharmacodynamic (PK/PD) analysis. Population PK model was built using the data of 116 Chinese subjects, including 88 healthy young subjects, 12 healthy elderly subjects, and 16 patients with intra-abdominal anaerobic infection. PK/PD analysis was performed combining the minimuminhibitoryconcentrations (MICs) of levornidazole against 375 anaerobic strains. Four sequential dosing regimens (500 mg q12h, 1000 mg loading dose followed by 500 mg q12h, 750 mg q24h, and 1000 mg q24h) were evaluated in terms of cumulative fraction of response (CFR) and probability of target attainment (PTA) by Monte Carlo simulation. The concentration data of levornidazole and its active metabolites were adequately described by two- and one-compartment model, respectively. Body weight was identified as a significant covariate of levornidazole clearance. Simulations showed that satisfactory PTA (> 90%) was achieved for the four dosing regimens when MIC ≤ 1 mg/L. Considering simulation results, patients' safety and compliance, levornidazole 750 mg IV infusion q24h for 2 days followed by oral dose of 750 mg q24h for 5 days was optimal for Bacteroides spp. with an identified MIC ≤ 1 mg/L.

The Real-World Clinical Impact of Plasma mNGS Testing: an Observational Study.

Plasma metagenomic next-generation sequencing (mNGS) testing is a promising diagnostic modality for infectious diseases, but its real-world clinical impact is poorly understood. We reviewed patients who had undergone plasma mNGS at a general hospital to evaluate the clinical utility of plasma mNGS testing. A total of 76.9% (113/147) of plasma mNGS tests had a positive result. A total of 196 microorganisms (58) were identified and reported, of which 75.6% (148/196) were clinically relevant. The median stringent mapped read number (SMRN) of clinically relevant organisms was 88 versus 22 for irrelevant organisms (P = 0.04). Based on the clinically adjudicated diagnosis, the positive and negative percent agreements of plasma mNGS testing for identifying a clinically defined infection were 95.2% and 67.4%, respectively. The plasma mNGS results led to a positive impact in 83 (57.1%) patients by diagnosing or ruling out infection and initiating targeted therapy. However, only 32.4% (11/34) of negative mNGS tests showed a positive impact, suggesting that plasma mNGS testing alone may not be a powerful tool to rule out infection in clinical practice. In the subset of 37 patients positive for both plasma mNGS and conventional testing, mNGS identified the pathogen(s) 2 days (IQR = 0.75 to 4.25) earlier than conventional testing. mNGS enables pathogen identification within 24 h, but given that the detection of clinically irrelevant organisms and nearly half of the tests result in no or a negative clinical impact, more clinical practice and studies are required to better understand who and when to test and how to optimally integrate mNGS into the infectious disease diagnostic workup. IMPORTANCE In this study, we show that although plasma mNGS testing significantly improved the detection rate of tested samples, nearly one in four (24.5%, 48/196) mNGS tests reported organisms were not clinically relevant, emphasizing the importance of cautious interpretation and infectious disease consultation. Moreover, based on clinical adjudication, plasma mNGS testing resulted in no or a negative impact in nearly half (43.5%, 64/147) of patients in the current study, indicating that how best to integrate this advanced method into current infectious disease diagnostic frameworks to maximize its clinical utility in real-world practice is an important question. Therefore, recommending plasma mNGS testing as a routine supplement to first-line diagnostic tests for infectious diseases faces great challenges. The decision to conduct mNGS testing should take into account the diagnostic performance, turnaround time and cost-effectiveness of mNGS, as well as the availability of conventional tests.

Should Paxlovid be prescribed for patients with severe COVID‐19 in the late course of infection? A case report

AbstractThe infection of the coronavirus disease 2019 (COVID‐19) is often accompanied by pneumonia with both high incidence and mortality. Paxlovid is commonly prescribed in patients with mild and normal pneumonia within 5 days from the symptom onset. Herein, we report a practically effective use of Paxlovid compensatively in patients with COVID‐19 and severe pneumonia after 5 days of infection in a typical case in China. In this case, a 75‐year‐old man was diagnosed with severe COVID‐19 complicated with a pulmonary bacterial infection. After treatment with oxygen inhalation, Cefoperazone‐sulbactam and ambroxol, fever and upper respiratory symptoms were alleviated, except for the Oxygenation index (OI) remaining worse, Coronavirus was detected as positive, and levels of interleukin‐6 remained high. Paxlovid was prescribed for 5 days subsequently though it was 14 days since symptom onset. Thereafter, the nucleic acid of the patient turned negative in 7 days and the symptoms resolved. This case showed that Paxlovid can be considered in patients with COVID‐19 and severe pneumonia even in the later course of infection in clinical practice in China.

Rapid quantification assay of hepatitis B virus DNA in human serum and plasma by Fully Automated Genetic Analyzer μTASWako g1.

Real-time monitoring of serum hepatitis B virus (HBV) levels is essential for the management of patients with chronic HBV infection in clinical practice, including monitoring the resistance of anti-HBV nucleotide analog or the detection of HBV reactivation. In this context, serum HBV deoxyribonucleic acid (DNA) quantification should be rapidly measured. A rapid HBV DNA quantification assay was established on the Fully Automated Genetic Analyzer, μTASWako g1. The assay performs automated sample preparation and DNA extraction, followed by the amplification and detection of quantitative polymerase chain reaction (PCR) combined with capillary electrophoresis (qPCR-CE) on integrated microfluidic chip. This study aimed to evaluate the analytical and clinical performance of HBV DNA assay on the μTASWako g1 platform in human serum and EDTA-plasma. The HBV DNA assay has a linear quantitative range from 20 to 108 IU/mL of HBV DNA with standard deviation (SD) of ≤0.14 log10 IU/mL. The limits of detection of the assay were 4.18 for the serum and 4.35 for EDTA-plasma. The HBV assay demonstrated the equivalent performance in both human serum and EDTA-plasma matrices. The HBV genotypes A to H were detected with an accuracy of ±0.34 log10 IU/mL. In quantification range, the HBV DNA assay was correlated with Roche cobas AmpliPrep/cobas TaqMan Ver2.0 (CAP/CTM v2) (r = 0.964). The mean difference (μTASWako g1-CAP/CTM v2) of the reported HBV DNA was -0.01 log10 IU/mL. Overall, the sensitivity, accuracy, and precision of the μTASWako g1 HBV assay were comparable to the existing commercial HBV DNA assay, and the assay can be completed within 110 min. This evaluation suggests that the HBV DNA assay on the μTASWako g1 is potentially applied for alternative method of the HBV viral load test, in particular with the advantage of the HBV DNA result availability within 2 h, improving the HBV infection management.