Current Opinion in Infectious Diseases最新文献

{"title":"Evidence supporting the use of therapeutic drug monitoring of ganciclovir in transplantation.","authors":"Diana D Wong,&nbsp;Su Ann Ho,&nbsp;Ana Domazetovska,&nbsp;Michelle K Yong,&nbsp;William D Rawlinson","doi":"10.1097/QCO.0000000000000965","DOIUrl":"10.1097/QCO.0000000000000965","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review describes current knowledge of ganciclovir (GCV) and valganciclovir (ValGCV) pharmacokinetic/pharmacodynamic characteristics, highlighting the likely contribution from host genetic factors to interpatient variability. The evidence and challenges surrounding optimization of drug dosing through therapeutic drug monitoring (TDM) are examined, with recommendations made.</p><p><strong>Recent findings: </strong>Pharmacokinetic studies of current dosing guidelines have shown high interindividual and intraindividual variability of GCV concentrations. This is sometimes associated with a slow decline in cytomegalovirus (CMV) viral load in some transplant recipients. A high incidence of GCV-associated myelosuppression has limited the use of this drug in the transplant setting. Patient groups identified to benefit from GCV TDM include pediatric patients, cystic fibrosis with lung transplantation, obese with kidney transplantation, and patients with fluctuating renal function or on hemodialysis. The emergence of refractory resistant CMV, particularly in immune compromised patients, highlights the importance of appropriate dosing of these antivirals. Host genetic factors need to be considered where recently, two host genes were shown to account for interpatient variation during ganciclovir therapy. Therapeutic Drug Monitoring has been shown to improve target antiviral-level attainment. The use of TDM may guide concentration-based dose adjustment, potentially improving virological and clinical outcomes. However, evidence supporting the use of TDM in clinical practice remains limited and further study is needed in the transplant cohort.</p><p><strong>Summary: </strong>Further studies examining novel biomarkers are needed to guide target concentrations in prophylaxis and treatment. The use of TDM in transplant recipients is likely to improve the clinical efficacy of current antivirals and optimize outcomes in transplant recipients.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"505-513"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41115952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory syncytial virus in children: epidemiology and clinical impact post-COVID-19.","authors":"Emily Rice,&nbsp;Daniel B Oakes,&nbsp;Charlie Holland,&nbsp;Hannah C Moore,&nbsp;Christopher C Blyth","doi":"10.1097/QCO.0000000000000967","DOIUrl":"10.1097/QCO.0000000000000967","url":null,"abstract":"<p><strong>Purpose of review: </strong>Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies.</p><p><strong>Recent findings: </strong>An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required.</p><p><strong>Summary: </strong>mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"522-528"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDR/XDR/PDR or DTR? Which definition best fits the resistance profile of Pseudomonas aeruginosa?","authors":"Federica Cosentino, Pierluigi Viale, Maddalena Giannella","doi":"10.1097/QCO.0000000000000966","DOIUrl":"10.1097/QCO.0000000000000966","url":null,"abstract":"<p><strong>Purpose of review: </strong>The aim of this narrative review is to compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs. established definitions in patients with Pseudomonas aeruginosa infection to understand the therapeutic implications of resistance classification and its impact on clinical outcome.</p><p><strong>Recent findings: </strong>Among Gram-negative bacteria (GNB), P. aeruginosa (PA) is associated with high rates of morbidity and mortality, mostly related to its intrinsic capacity of developing antibiotic resistance. Several classifications of antibiotic resistance have been proposed in the last 15 years. The most common used is that from Magiorakos et al. including multidrug resistance (MDR), extensively drug-resistant (XDR) and pan drug resistance (PDR) according to the number of antibiotic classes showing in vitro activity. A further classification based on the resistance to specific antibiotic classes (i.e. fluoroquinolones, cephalosporins, carbapenem resistance) was also proposed. However, both of them have been criticized because of limited usefulness in clinical practice and for poor correlation with patient outcome, mainly in infections due to PA. More recently the new definition of difficult-to-treat resistance (DTR) has been proposed referring to nonsusceptibility to all first-line agents showing high-efficacy and low-toxicity (i.e. carbapenems, β-lactam-β-lactamase inhibitor combinations, and fluoroquinolones). Studies including large cohorts of patients with GNB bloodstream infections have confirmed the prognostic value of DTR classification and its clinical usefulness mainly in infections due to PA. Indeed, in the recent documents from the Infectious Diseases Society of America (IDSA) on the management of antibiotic resistant GNB infections, the DTR classification was applied to PA.</p><p><strong>Summary: </strong>DTR definition seems to identify better than MDR/XDR/PDR and single class resistant categories the cases of PA with limited treatment options. It requires periodic revision in order to remain up-to-date with the introduction of new antibiotics and the evolving pattern of resistance.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":"36 6","pages":"564-571"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using antibiotics wisely.","authors":"Jae Jung,&nbsp;Francesca Cozzi,&nbsp;Graeme N Forrest","doi":"10.1097/QCO.0000000000000973","DOIUrl":"10.1097/QCO.0000000000000973","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review will describe role of shorter antibiotic therapies, early switch from intravenous to oral therapy, and artificial intelligence in infectious diseases.</p><p><strong>Recent findings: </strong>There is evidence that shorter courses of antibiotics are noninferior to standard durations of therapy. This has been demonstrated with Enterobacterales bacteremia that can be treated with 7 days of therapy, community acquired pneumonia with 3 days and ventilator associated pneumonia with just 7 days of antibiotic therapy. The conversion from intravenous to oral therapy in treating bacteremia, endocarditis and bone and joint infections is safe and effective and reduces line complications and costs. Also, for clean surgical procedures only one dose of antibiotic is needed, but it should be the most effective antibiotic which is cefazolin. This means avoiding clindamycin, removing penicillin allergies where possible for improved outcomes. Finally, the role of artificial intelligence to incorporate into using antibiotics wisely is rapidly emerging but is still in early stages.</p><p><strong>Summary: </strong>In using antibiotics wisely, targeting such as durations of therapy and conversion from intravenous antibiotic therapy to oral are low hanging fruit. The future of artificial intelligence could automate a lot of this work and is exciting but needs to be proven.</p><p><strong>Video abstract: </strong>http://links.lww.com/COID/A50.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"462-472"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention and treatment of C. difficile in cancer patients.","authors":"Pedro Puerta-Alcalde,&nbsp;Carolina Garcia-Vidal,&nbsp;Alex Soriano","doi":"10.1097/QCO.0000000000000954","DOIUrl":"10.1097/QCO.0000000000000954","url":null,"abstract":"<p><strong>Purpose of review: </strong>We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients.</p><p><strong>Recent findings: </strong>Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates.</p><p><strong>Summary: </strong>Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"473-480"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment approaches for severe Stenotrophomonas maltophilia infections.","authors":"Maria F Mojica,&nbsp;Robert A Bonomo,&nbsp;David van Duin","doi":"10.1097/QCO.0000000000000975","DOIUrl":"10.1097/QCO.0000000000000975","url":null,"abstract":"<p><strong>Purpose of review: </strong>Stenotrophomonas maltophilia is an emerged opportunistic pathogen. Intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Herein, we provide an update on the most recent literature on treatment options for severe S. maltophilia infections.</p><p><strong>Recent findings: </strong>Trimethoprim-sulfamethoxazole (SXT) is recognized as the first-line therapy for S. maltophilia infections. However, its clinical use is based on good in vitro activity and favorable clinical outcomes, rather than on solid minimum inhibitory concentration (MIC) correlations with pharmacokinetic/pharmacodynamics (PK/PD) and/or clinical outcomes. The same is true for other treatment options like levofloxacin (LVX) and minocycline (MIN). Recent PK/PD studies question the current clinical breakpoints for SXT, LVX, and MIN. Based on this, the latest guidance issued by the Infectious Diseases Society of America (IDSA) recommends using these agents only as part of a combination therapy. Alternatively, novel therapeutic options such as cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM) are suggested, based on limited but promising clinical data.</p><p><strong>Summary: </strong>PK/PD data and controlled clinical studies are needed to optimize current treatment options. Presently, combination therapy of SXT, LVX, MIN, or FDC, or monotherapy with CZA-ATM are recommended therapeutic options for severe-to-moderate S. maltophilia infections.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"572-584"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of nonfermenting gram-negative infections: a critique of the guidelines.","authors":"Matteo Bassetti,&nbsp;Antonio Vena,&nbsp;Daniele Roberto Giacobbe","doi":"10.1097/QCO.0000000000000982","DOIUrl":"10.1097/QCO.0000000000000982","url":null,"abstract":"<p><strong>Purpose of review: </strong>In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections.</p><p><strong>Recent findings: </strong>Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel β-lactams and β-lactam/β-lactamase inhibitor combinations.</p><p><strong>Summary: </strong>A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"609-614"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucormycosis: update on clinical presentation, diagnosis, and treatment.","authors":"Natalie J M Dailey Garnes,&nbsp;Dimitrios P Kontoyiannis","doi":"10.1097/QCO.0000000000000976","DOIUrl":"10.1097/QCO.0000000000000976","url":null,"abstract":"<p><strong>Purpose of review: </strong>Mucormycosis (MCR) is a common opportunistic mold infection, and Mucorales were recently designated by WHO as priority pathogens. The interest in this infection has risen significantly since the major outbreak of MCR in the context of the COVID-19 pandemic, particularly in India. Herein, we summarize recently (last 24 months) published information regarding clinical aspects of MCR.</p><p><strong>Recent findings: </strong>The disease remains protean in its clinical presentation, difficult to diagnose, and challenging to treat. In 2021, cases of COVID-19-associated mucormycosis (CAM) exploded in India during COVID-19 and manifested primarily as sino-orbital or sino-cerebral disease. Its classic risk factors included the triad of COVID-19, uncontrolled diabetes mellitus and use of corticosteroids. Despite difficulties in the timely diagnosis of MCR, significant progress has been made with the use of molecular techniques in blood to assist with earlier diagnosis, which can facilitate earlier appropriate therapy and improve outcomes. In addition, advances have been made in the use of imaging to stage the disease, determining what types of multimodal therapy are required depending on staging, and tissue-based identification of Mucorales.</p><p><strong>Summary: </strong>Although the outlook for MCR has improved, effective new antifungals, risk stratification, and the optimal multimodality approaches remain an unmet need.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"427-435"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41115071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management strategies for severe Pseudomonas aeruginosa infections.","authors":"Hermann Do Rego, Jean-François Timsit","doi":"10.1097/QCO.0000000000000981","DOIUrl":"10.1097/QCO.0000000000000981","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review focuses on the management of severe Pseudomonas aeruginosa infections in critically ill patients.</p><p><strong>Recent findings: </strong>Pseudomonas aeruginosa is the most common pathogen in intensive care; the main related infections are nosocomial pneumonias, then bloodstream infections. Antimicrobial resistance is common; despite new antibiotics, it is associated with increased mortality, and can lead to a therapeutic deadlock.</p><p><strong>Summary: </strong>Carbapenem resistance in difficult-to-treat P. aeruginosa (DTR-PA) strains is primarily mediated by loss or reduction of the OprD porin, overexpression of the cephalosporinase AmpC, and/or overexpression of efflux pumps. However, the role of carbapenemases, particularly metallo-β-lactamases, has become more important. Ceftolozane-tazobactam, ceftazidime-avibactam and imipenem-relebactam are useful against DTR phenotypes (noncarbapenemase producers). Other new agents, such as aztreonam-ceftazidime-avibactam or cefiderocol, or colistin, might be effective for carbapenemase producers. Regarding nonantibiotic agents, only phages might be considered, pending further clinical trials. Combination therapy does not reduce mortality, but may be necessary for empirical treatment. Short-term treatment of severe P. aeruginosa infections should be preferred when it is expected that the clinical situation resolves rapidly.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"585-595"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What is the clinical significance of 'heteroresistance' in nonfermenting Gram-negative strains?","authors":"Giusy Tiseo,&nbsp;Valentina Galfo,&nbsp;Marco Falcone","doi":"10.1097/QCO.0000000000000964","DOIUrl":"10.1097/QCO.0000000000000964","url":null,"abstract":"<p><strong>Purpose of review: </strong>The aim of this study was to discuss the potential clinical significance of heteroresistance in nonfermenting Gram-negative bacilli (GNB).</p><p><strong>Recent findings: </strong>Recently, heteroresistance has been considered potentially responsible for clinical failure in Acinetobacter baumannii infections. This raised a scientific debate, still open, about the potential clinical significance of heteroresistance in nonfermenting GNB.</p><p><strong>Summary: </strong>We reviewed the literature of last 20 years and found a limited number of studies evaluating the relationship between heteroresistance and clinical outcome in nonfermenting GNB. Unlike Gram-positive bacteria, heteroresistance is reported in a significant proportion of nonfermenting GNB with some studies describing it in all tested strains and for several antibiotics (including tigecycline, carbapenems, levofloxacin, cefiderocol, colistin). One important issue is the need for validated detection method since the population analysis profile test, that is considered the gold standard, requires high costs and time. Studies evaluating the correlation between heteroresistance and clinical outcome are contrasting and have several limitations. Although in-vitro detection of heteroresistance in nonfermenting GNB has not been associated with in-vivo treatment failure, its presence may suggest to prefer combination regimens instead monotherapy when treating infections by nonfermenters. Further studies are needed to clarify the clinical significance of heteroresistance.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":" ","pages":"555-563"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}