Infectious Diseases and Therapy最新文献

Introduction: Infective endocarditis (IE) due to methicillin-resistant Staphylococcus aureus (MRSA) is characterized by frequent treatment failure to first-line agents and high mortality, necessitating use of alternative management strategies. Ceftaroline fosamil (CPT) is a cephalosporin antibiotic with activity against MRSA but without regulatory approval for the indication of IE. This study describes clinical experience with CPT-based regimens utilized in MRSA-IE.

Methods: This is a retrospective, observational, descriptive analysis of patients from two major urban medical centers in Detroit, Michigan from 2011 to 2023. Included adult patients (≥ 18 years) had ≥ 1 positive blood culture for MRSA, met definitive clinical criteria for IE, and received CPT for ≥ 72 h. The primary outcome was treatment failure, defined as a composite of 30-day all-cause mortality from index culture or failure to improve or resolve infectious signs/symptoms after CPT initiation.

Results: Seventy patients were included. The median (interquartile range [IQR]) age was 51 (34-63) years and 45.7% were male. Persons with injection drug use (PWID) made up 55.7% of the cohort and right-sided IE was the most prevalent subtype (50.0%). CPT was frequently employed second-line or later, often in combination with vancomycin (10.0%) or daptomycin (72.9%). Overall, 31.4% experienced treatment failure and 30-day all-cause mortality occurred in 15.7%.

Conclusions: These findings illustrate the challenges posed by MRSA-IE, including frequent treatment failures, and highlight the utilization of CPT as salvage therapy. Comparative studies are needed to more clearly define its role in MRSA-IE.

Introduction: Health claims data are a valuable resource for health services research, enabling analysis of the costs of hospitalizations, outpatient visits, procedures, and medications, and providing an improved understanding of the economic burden and underlying cost drivers for a given health condition. Since no recent data were available from Germany on the medical costs and clinical outcomes of Clostridioides difficile infections (CDI), this study assessed the economic burden of CDI and all-cause mortality in adults in Germany.

Methods: A retrospective cohort study was conducted using a large, anonymized administrative health claims research database from Germany from which an age- and sex-representative sample of 4 million insured persons covered by approximately 60 statutory health insurances was extracted. Propensity score matching was conducted on age, sex, comorbidities, and antibiotic use to identify four matched controls (i.e., patients without CDI) for every eligible adult patient with CDI (i.e., case) in the study cohort. Costs, healthcare resource utilization, and CDI-attributable all-cause mortality were assessed.

Results: Overall, there were 15,342 CDI cases in the study cohort. One-year mortality in CDI cases (45.7%) was more than fourfold that of matched non-CDI controls (11.0%). In the year following the index date, average mortality-adjusted medical costs per person-time for CDI cases were almost fivefold that of matched non-CDI controls, representing a cost difference of €31,459, mainly driven by inpatient treatment. Overall excess costs for CDI cases were estimated at approximately €1.6 billion within 1 year after diagnosis.

Conclusions: CDI in Germany is associated with a high clinical and economic burden, including significantly higher mortality, costs, and healthcare resource utilization, in patients with CDI versus their matched patients without CDI. This has important implications for patients, healthcare providers, and the healthcare system.

Introduction: As no standard case definitions for respiratory syncytial virus-associated lower respiratory tract disease (RSV-LRTD) in adults are available, this study analyzed definitions for severe RSV-LRTD from previously published data in hospital and community cohorts of adults with RSV-associated symptoms.

Methods: The frequency, sensitivity, and specificity of acute respiratory disease symptoms among hospitalized and community cohorts of adults with RSV were analyzed. RSV-LRTD signs/symptoms assessed included shortness of breath (dyspnea), cough and/or fever, wheezing/rales/rhonchi (abnormal lung sounds by auscultation), sputum production, tachypnea, hypoxemia, and pleuritic chest pain.

Results: Dyspnea and tachypnea provided the best differentiation between hospitalized and community RSV-positive cases. The severe RSV-LRTD case definition yielding one of the highest and best-balanced sensitivity and specificity was dyspnea paired with either abnormal lung sounds by auscultation, hypoxemia, tachypnea, cough and/or fever, sputum, or chest pain.

Conclusions: Dyspnea alone, and in combination with certain other lower respiratory tract disease signs/symptoms, was a leading symptomatic indicator for severe RSV outcomes. These results contribute to the harmonization of case definitions for RSV disease.

Antimicrobial resistance is a significant global public health issue, and the dissemination of antibiotic resistance in Gram-positive bacterial pathogens has significantly increased morbidity, mortality rates, and healthcare costs. Among them, Staphylococcus, especially methicillin-resistant Staphylococcus aureus (MRSA), causes a wide range of diseases due to its diverse pathogenic factors and infection strategies. These bacteria also present significant issues in veterinary medicine and food safety. Effectively managing staphylococci-related problems necessitates a concerted effort to implement preventive measures, rapidly detect the pathogen, and develop new and safe antimicrobial therapies. In recent years, there has been growing interest in using endolysins to combat bacterial infections. These enzymes, which are also referred to as lysins, are a unique class of hydrolytic enzymes synthesized by double-stranded DNA bacteriophages. They possess glycosidase, lytic transglycosylase, amidase, and endopeptidase activities, effectively destroying the peptidoglycan layer and resulting in bacterial lysis. This unique property makes endolysins powerful antimicrobial agents, particularly against Gram-positive organisms with more accessible peptidoglycan layers. Therefore, considering the potential benefits of endolysins compared to conventional antibiotics, we have endeavored to gather and review the characteristics and uses of endolysins derived from staphylococcal bacteriophages, as well as their antibacterial effectiveness against Staphylococcus spp. based on conducted experiments and trials.

Introduction: There remains uncertainty about whether transitioning to oral antibiotic therapy is appropriate for the management of children with methicillin-resistant Staphylococcus aureus (MRSA) bacteremic osteomyelitis. We compared clinical outcomes for children with MRSA osteomyelitis with associated bacteremia who were transitioned to discharge oral antibiotic therapy to those discharged on outpatient parenteral antibiotic therapy (OPAT).

Methods: We performed a retrospective, multicenter, cohort study of children ≤ 18 years hospitalized with MRSA bacteremic osteomyelitis across four children's hospitals from 2007 to 2018 discharged on oral antibiotic therapy versus OPAT. The primary outcome was treatment failure within 6 months of discharge, defined as any of the following: diagnosis of chronic osteomyelitis, conversion from oral to IV antibiotic route, an operative procedure after the index hospitalization (abscess drainage, bone biopsy, arthrocentesis, or pathologic fracture) and/or recrudescence of MRSA bacteremia. Outcomes were analyzed in an inverse propensity score weighted (IPW) cohort.

Results: A total of 106 cases of MRSA bacteremic osteomyelitis were included; 44 (42%) were discharged in the oral antibiotic therapy group and 62 (59%) patients were discharged in the OPAT group. In the IPW cohort, treatment failure within 6 months of discharge occurred in 3.4% of children in the discharge oral therapy group and 16.3% in the OPAT group (P = 0.03). The odds of 6-month composite treatment failure between discharge oral therapy and OPAT were 0.18 (95% CI 0.05-0.61).

Conclusions: Discharge oral therapy was not associated with higher rates of treatment failure compared to OPAT for children with MRSA bacteremic osteomyelitis.

Introduction: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US.

Methods: A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements.

Results: Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%-96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%-69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups.

Conclusion: Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians.

Introduction: Lower respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) is common among young children in Argentina. Use of the currently available prophylactic agent is limited to children aged ≤ 2 years with selected high-risk conditions, and thus the majority of infants remain unprotected. We estimated the value-based price (VBP) of a novel RSVpreF vaccine for use among pregnant people for prevention of RSV-LRTI among infants during the first year of life.

Methods: Clinical outcomes and economic costs of RSV-LRTI during infancy and expected impact of RSVpreF vaccination during pregnancy were projected using a population-based Markov-type cohort model. Model results-estimated on the basis of gestational age at birth, disease/fatality rates, and mother's vaccination status-include total numbers of RSV-LRTI cases, RSV-LRTI-related deaths, and associated costs. Base case analyses (RSVpreF vs. no vaccine) were conducted from the healthcare system perspective. Probabilistic sensitivity analyses (PSA; 1000 replications) were also conducted. Willingness-to-pay (WTP) was $10,636 per quality-adjusted life-year (QALY; i.e., 1 × 2021 gross domestic product [GDP] per capita) in base case analyses and PSA. Costs are reported in USD, estimated on the basis of the June 22, 2023 exchange rate.

Results: Use of RSVpreF among 342,110 pregnant persons provided protection to 330,079 infants at birth. In total, RSVpreF prevented 3915 RSV hospitalizations, 6399 RSV cases requiring emergency department care, 6182 RSV cases requiring a physician office visit, and 67 disease-related deaths. Direct costs were projected to be reduced by $5.0 million. With 2061 QALYs gained and vaccine administration cost of $1.4 million, the VBP of RSVpreF was estimated to be $74.46 per dose. In PSA, mean VBP was $75.02 (95% confidence interval 54.24-97.30).

Conclusions: RSVpreF among pregnant persons would significantly reduce the clinical and economic burden of RSV-LRTI among infants in Argentina and would be considered a cost-effective intervention up to a price of approximately $75.

The spread of carbapenemase-producing gram-negative pathogens, especially those producing metallo-β-lactamases (MBLs), has become a major health concern. MBLs are molecularly the most diverse carbapenemases, produced by a wide spectrum of gram-negative organisms, including the Enterobacterales, Pseudomonas spp., Acinetobacter baumannii, and Stenotrophomonas maltophilia, and can hydrolyze most β-lactams using metal ion cofactors in their active sites. Over the years, the prevalence of MBL-carrying isolates has increased globally, particularly in Asia. MBL infections are associated with adverse clinical outcomes including longer length of hospital stay, ICU admission, and increased mortality across the globe. The optimal treatment for MBL infections not only depends on the pathogen but also on the underlying resistance mechanisms. Currently, there are only few drugs or drug combinations that can efficiently offset MBL-mediated resistance, which makes the treatment of MBL infections challenging. The rising concern of MBLs along with the limited treatment options has led to the need and development of drugs that are specifically targeted towards MBLs. This review discusses the prevalence of MBLs, their clinical impact, and the current treatment options for MBL infections and their limitations. Furthermore, this review will discuss agents currently in the pipeline for treatment of MBL infections.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice.

Methods: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system.

Results: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance.

Conclusions: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence.

Introduction: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls.

Methods: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models.

Results: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19.

Conclusions: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6-24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.