Infectious Diseases (all articles)
Review: Acute Respiratory Distress Syndrome
28 Nov, 2024 | 13:06h | UTCIntroduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition characterized by diffuse alveolar damage, leading to hypoxemia and respiratory failure. Since its initial description in 1967, the understanding and definition of ARDS have significantly evolved, integrating advances in basic science and clinical practice. A newly recommended global definition expands diagnostic criteria to enhance early recognition and management, especially in resource-limited settings. This review summarizes current insights into the epidemiology, pathophysiology, and evidence-based management of ARDS, highlighting key updates and future research priorities.
Key Recommendations:
- New Global Definition of ARDS: Adoption of an expanded definition that includes patients receiving high-flow nasal oxygen (HFNO) support and allows diagnosis using pulse oximetry and thoracic ultrasonography. This makes ARDS identification feasible in diverse clinical environments, including those with limited resources.
- Established Critical Care Interventions: Emphasis on early implementation of proven strategies such as low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cm H₂O, prone positioning for patients with PaO₂/FiO₂ <150 mm Hg, and conservative fluid management after initial resuscitation. These interventions have consistently reduced mortality and are recommended as standard care.
- Personalized Approaches and Phenotyping: Recognition of the heterogeneity in ARDS pathophysiology underscores the need for personalized treatment strategies. Identification of hyper-inflammatory and hypo-inflammatory phenotypes may guide targeted therapies and improve outcomes, although prospective validation is required.
- Impact of COVID-19 on ARDS: Acknowledgment of the significant increase in ARDS incidence due to the COVID-19 pandemic. While COVID-19 ARDS shares similarities with traditional ARDS, notable differences in endothelial dysfunction and immune response highlight the necessity for tailored management approaches in these patients.
- Pharmacologic Interventions: Updated guidelines provide conditional recommendations for the use of corticosteroids in ARDS, particularly in early moderate to severe cases. Ongoing research into pharmacologic agents such as statins, mesenchymal stromal cells, and other cell-based therapies shows potential but requires further clinical trials to establish efficacy.
- Future Research Priorities: Identification of key areas for investigation, including the long-term sequelae of ARDS, optimization of non-invasive and invasive ventilation strategies, exploration of genetic and environmental risk factors, and development of rapid biomarker assays for real-time phenotyping and targeted therapy.
Conclusion: The evolving definition and understanding of ARDS aim to improve early detection and standardization of care across various clinical settings. Reinforcing established critical care interventions while advancing personalized and novel therapeutic approaches holds promise for reducing mortality and enhancing long-term patient outcomes. Continuous research into the pathophysiology and management of ARDS, enriched by insights from the COVID-19 pandemic, is essential to address ongoing challenges and improve patient care.
RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background
28 Nov, 2024 | 12:38h | UTCBackground: Although preexposure prophylaxis (PrEP) effectively reduces HIV transmission, adherence to daily oral regimens is suboptimal among high-risk populations. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, has shown efficacy in cisgender women, but its efficacy in men and gender-diverse individuals remains unclear.
Objective: To evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir compared to background HIV incidence and daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among men and gender-diverse persons.
Methods: In this phase 3, double-blind, randomized trial, 3,271 HIV-negative participants were assigned in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral F/TDF, with matching placebos. Participants were cisgender men, transgender women and men, and gender-nonbinary persons aged 16 or older who have sex with male-assigned partners. The primary endpoint compared HIV incidence in the lenacapavir group to background incidence; secondary analysis compared lenacapavir to F/TDF.
Results: In the modified intention-to-treat analysis (n=3,265), HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). The background HIV incidence was 2.37 per 100 person-years. Lenacapavir significantly reduced HIV incidence compared to background (incidence rate ratio [IRR], 0.04; 95% CI, 0.01–0.18; P<0.001) and F/TDF (IRR, 0.11; 95% CI, 0.02–0.51; P=0.002). No significant safety concerns emerged. Injection-site reactions led to discontinuation in 1.2% of lenacapavir recipients and 0.3% of F/TDF recipients.
Conclusions: Twice-yearly subcutaneous lenacapavir significantly reduced HIV incidence compared to both the background incidence and daily oral F/TDF among men and gender-diverse persons. These findings support lenacapavir as an effective PrEP option in this population.
Implications for Practice: The introduction of a long-acting, twice-yearly injectable PrEP option like lenacapavir could improve adherence and uptake among populations challenged by daily oral regimens.
Study Strengths and Limitations: Strengths include a large, diverse participant population with significant representation of transgender and gender-nonbinary persons, and the use of an active comparator. The novel counterfactual design estimating background HIV incidence avoided ethical issues of placebo controls but may have limitations in accuracy. Limitations include a relatively short follow-up and potential impact of injection-site reactions on adherence. The emergence of resistance mutations in participants who acquired HIV while on lenacapavir is a concern needing further investigation.
Future Research: Further studies should assess the long-term safety, efficacy, and resistance patterns associated with lenacapavir use. Research into optimizing injection techniques to minimize injection-site reactions and exploring lenacapavir’s applicability in other at-risk populations is recommended.
Review: Candida auris Infections
24 Nov, 2024 | 19:50h | UTCIntroduction: Candida auris, first identified in Japan in 2009, has rapidly emerged as a global public health threat due to its multidrug resistance and propensity to cause difficult-to-control outbreaks in healthcare settings. This review by Lionakis and Chowdhary aims to provide clinicians with an in-depth understanding of the mycologic features, immune responses, epidemiology, risk factors, clinical manifestations, diagnosis, antifungal resistance, treatment, and prevention strategies associated with C. auris infections to inform effective patient care and containment measures.
Key Points:
- Mycologic Features: C. auris is a budding yeast that thrives in high-salt and high-temperature environments. It is divided into five clades (I–V) with distinct geographic distributions and varying virulence and resistance profiles.
- Immune Response: The interleukin-17 pathway is crucial in reducing skin colonization by C. auris, while phagocytes like monocytes, macrophages, and neutrophils are essential for clearing bloodstream and organ infections.
- Epidemiology: Reported in over 45 countries, C. auris is known for causing outbreaks in healthcare facilities due to its persistence on skin and surfaces and challenges in accurate identification. The CDC classifies it as an urgent threat, and the WHO places it in the “critical” group of human fungal pathogens.
- Risk Factors: Key risk factors include advanced age, indwelling medical devices, immunocompromised states, diabetes, recent surgery, use of broad-spectrum antibiotics or antifungals, prolonged hospitalization, and severe COVID-19.
- Clinical Manifestations: Primarily causing invasive infections like candidemia, C. auris is associated with high morbidity and mortality rates (30–60%). Up to 25% of critically ill colonized patients may develop invasive infections.
- Diagnosis: Accurate identification is challenging due to misidentification with other Candida species on conventional tests. Reliable methods include MALDI-TOF mass spectrometry, sequencing of rDNA regions, and molecular assays like PCR.
- Antifungal Resistance: C. auris exhibits clade-specific multidrug resistance, with most strains resistant to fluconazole and some resistant to echinocandins and amphotericin B. Resistance mechanisms involve mutations in the ERG11 and FKS1 genes.
- Treatment: Echinocandins are recommended as first-line treatment for invasive C. auris infections. Close monitoring is essential due to potential treatment failure and emergence of resistance. Amphotericin B formulations may be used in neonates or if echinocandin resistance is present.
- Prevention: Strict infection control measures are critical, including contact precautions, environmental cleaning with EPA-registered disinfectants effective against C. auris, surveillance screening, and cohorting of patients to prevent nosocomial transmission.
Conclusion: The rapid global spread of multidrug-resistant C. auris presents significant challenges for clinical management and infection control. Early and accurate diagnosis, appropriate antifungal therapy, and stringent prevention strategies are essential to improve patient outcomes and prevent further dissemination of this pathogen.
RCT: 7-Day Antibiotic Therapy Noninferior to 14-Day for Bloodstream Infections
20 Nov, 2024 | 18:19h | UTCBackground: Bloodstream infections are a significant cause of morbidity and mortality worldwide. Early and appropriate antibiotic therapy is essential, but the optimal duration remains uncertain. Prolonged antibiotic use can lead to adverse events, Clostridioides difficile infection, antimicrobial resistance, and increased healthcare costs.
Objective: To determine whether a 7-day course of antibiotic treatment is noninferior to a 14-day course in hospitalized patients with bloodstream infections regarding 90-day all-cause mortality.
Methods: In this multicenter, noninferiority randomized controlled trial, 3,608 hospitalized patients from 74 hospitals in seven countries were enrolled. Eligible patients had bloodstream infections but were excluded if they had severe immunosuppression, infections requiring prolonged therapy, possible contaminants, or Staphylococcus aureus bacteremia. Participants were randomized to receive either 7 days (n=1,814) or 14 days (n=1,794) of adequate antibiotic therapy, with antibiotic selection at the clinicians’ discretion. The primary outcome was death from any cause by 90 days post-diagnosis, with a noninferiority margin of 4 percentage points.
Results: At 90 days, mortality was 14.5% in the 7-day group and 16.1% in the 14-day group (difference: –1.6 percentage points; 95.7% CI, –4.0 to 0.8), demonstrating noninferiority of the shorter duration. Noninferiority was confirmed in per-protocol and modified intention-to-treat analyses. Secondary outcomes, including relapse rates, adverse events, and hospital length of stay, were similar between groups. Findings were consistent across subgroups based on infection source, pathogen type, and patient characteristics.
Conclusions: A 7-day antibiotic regimen is noninferior to a 14-day regimen for treating hospitalized patients with bloodstream infections, without increasing mortality or relapse rates.
Implications for Practice: Implementing a 7-day antibiotic course could reduce antibiotic exposure, minimize adverse events, and potentially limit antimicrobial resistance development. Clinicians should consider individual patient factors, such as infection severity and comorbidities, before universally adopting shorter treatment durations.
Study Strengths and Limitations: Strengths include a large, diverse patient population and inclusion of critically ill patients, enhancing generalizability. Limitations involve the open-label design and nonadherence to assigned durations in some cases (23.1% in the 7-day group continued antibiotics longer). Exclusion of S. aureus bacteremia limits applicability to that subgroup. The study may not have been powered to detect differences in rare adverse outcomes like C. difficile infection or antimicrobial resistance emergence.
Future Research: Further studies should explore the efficacy of even shorter antibiotic durations, individualized treatment strategies based on patient response, and the long-term impact on antimicrobial resistance and healthcare costs.
Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients
16 Nov, 2024 | 17:29h | UTCBackground: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.
Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.
Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.
Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).
Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.
Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.
Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.
Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.
Retrospective Cohort Study: Midline Catheters Associated with Lower Major Complications Than PICCs in Outpatient Antimicrobial Therapy
16 Nov, 2024 | 14:35h | UTCBackground: Outpatient parenteral antimicrobial therapy (OPAT) requires reliable vascular access for administering intravenous antibiotics post-hospitalization. Peripherally inserted central catheters (PICCs) are commonly used due to their versatility and ease of placement. Recently, midline catheters have emerged as potential alternatives for OPAT, offering less invasive access. However, limited evidence exists comparing the safety and complication rates of midline catheters versus PICCs in OPAT patients.
Objective: To compare the risk of major and minor device complications associated with midline catheters versus PICCs in patients receiving OPAT.
Methods: This retrospective cohort study analyzed data from 2,824 hospitalized patients across 69 Michigan hospitals who received either a midline catheter (n=1,999) or a PICC (n=825) for OPAT between January 2017 and November 2023. Patients receiving vancomycin were excluded. The primary outcome was major device complications, defined as catheter-related bloodstream infection (CRBSI) or catheter-related venous thromboembolism (CR-VTE). Secondary outcomes included minor device complications (e.g., catheter dislodgement, occlusion) and device failure, defined as catheter removal due to any complication.
Results: Midline catheters were associated with a lower risk of major complications compared to PICCs (0.8% vs 3.4%; adjusted hazard ratio [aHR], 0.46; 95% CI, 0.23-0.91; P < .001). This difference was more pronounced for devices with dwell times of 14 days or fewer (aHR, 0.29; 95% CI, 0.12-0.68). There were no significant differences in minor complications (10.3% vs 13.8%; aHR, 1.07; 95% CI, 0.83-1.38) or device failure rates (9.6% vs 12.1%; aHR, 1.26; 95% CI, 0.96-1.65) between midline catheters and PICCs.
Conclusions: Midline catheters are associated with a lower risk of major complications compared to PICCs in patients receiving OPAT, particularly for treatment durations of 14 days or fewer. These findings suggest that midline catheters are a safe and effective alternative to PICCs for short-term OPAT.
Implications for Practice: Clinicians should consider using midline catheters for OPAT when the anticipated therapy duration is 14 days or less and the infusate is peripherally compatible. This may reduce the risk of major complications such as CRBSI and CR-VTE, potentially improving patient outcomes and reducing healthcare costs.
Study Strengths and Limitations: Strengths of this study include a large, diverse patient population across multiple hospitals and rigorous data collection methods. Limitations include its retrospective design, potential for unmeasured confounding, and exclusion of patients receiving vancomycin, which may limit generalizability. Additionally, complications occurring after 30 days or post-device removal may have been missed.
Future Research: Further studies are needed to evaluate the safety and efficacy of midline catheters for OPAT durations exceeding 14 days and to explore factors influencing long-term device performance and patient outcomes.
Test-Negative Study: RSV Vaccine May Reduce Hospitalizations and ED Visits in Adults Aged ≥60
16 Nov, 2024 | 14:18h | UTCBackground: Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality among older adults in the USA, with an estimated 100,000–160,000 RSV-associated hospitalizations annually in those aged 60 years and older. In 2023, RSV vaccines were recommended for this population, showing efficacy in clinical trials. However, real-world effectiveness data, particularly against severe outcomes like hospitalizations in high-risk groups, are limited.
Objective: To assess the real-world effectiveness of RSV vaccination against RSV-associated hospitalizations and emergency department (ED) encounters among adults aged 60 years and older during the 2023–24 RSV season in the USA.
Methods: A test-negative design analysis was conducted using data from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION), encompassing eight states. Adults aged ≥60 presenting with RSV-like illness and tested for RSV from Oct 1, 2023, to Mar 31, 2024, were included. Vaccination status was determined through electronic health records, immunization registries, and medical claims. Vaccine effectiveness (VE) was estimated by comparing the odds of vaccination among RSV-positive cases and RSV-negative controls, adjusting for age, sex, race and ethnicity, comorbidities, and geographic region.
Results: Among 28,271 hospitalizations for RSV-like illness in immunocompetent adults aged ≥60, VE against RSV-associated hospitalization was 80% (95% CI 71–85). VE against RSV-associated critical illness (ICU admission or death) was 81% (95% CI 52–92). In 8,435 hospitalizations among immunocompromised adults, VE was 73% (95% CI 48–85) against RSV-associated hospitalization. Among 36,521 ED encounters in immunocompetent adults, VE against RSV-associated ED visits was 77% (95% CI 70–83). VE estimates were consistent across age groups and vaccine products.
Conclusions: RSV vaccination effectively prevented RSV-associated hospitalizations and ED visits among adults aged ≥60 during the first season post-approval, including those at highest risk due to advanced age or immunocompromise.
Implications for Practice: These findings support recommending RSV vaccination for adults aged ≥60 to reduce severe RSV-related morbidity and mortality. Clinicians should consider advising eligible patients to receive the RSV vaccine to prevent hospitalizations and critical illness.
Study Strengths and Limitations: Strengths include a large, geographically diverse cohort and integrated medical, laboratory, and vaccination data, allowing robust VE estimates across subgroups. Limitations involve potential misclassification of vaccination status, residual confounding, and reliance on clinician-directed RSV testing, which may introduce bias.
Future Research: Further studies are needed to evaluate the duration of vaccine protection over multiple RSV seasons and to assess VE in other high-risk populations and settings.
Review: Lung Transplantation
16 Nov, 2024 | 13:33h | UTCIntroduction: Lung transplantation has progressed from experimental to standard therapy for life-threatening lung diseases, offering improved survival and quality of life. Challenges include primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, and long-term immunosuppression effects. This review highlights current practices, developments, and opportunities to enhance this transformative therapy.
Key Recommendations
- Candidate Selection: Selection criteria have shifted from strict contraindications to a holistic approach emphasizing physiologic age, frailty, and recoverability. Early referral and multidisciplinary assessment are recommended to address barriers and optimize outcomes.
- Donor-Lung Utilization: Extended-criteria donors, including older donors and those with smoking histories, are increasingly used. Ex vivo lung perfusion allows detailed lung assessment and reconditioning, while antiviral therapies enable transplantation of lungs from hepatitis C-positive donors.
- Lung Allocation: Urgency-weighted scores prioritize factors like medical urgency and post-transplant survival. Recent updates include biologic disadvantages, patient access, and logistical efficiency to improve fairness and outcomes.
- Surgical Techniques: Bilateral sequential lung transplantation is standard, with ECMO replacing cardiopulmonary bypass in many cases. Surgical approaches are tailored to individual needs, with options like volume reduction or lobectomy for size mismatches.
- Postoperative Management: Primary graft dysfunction affects up to 25% of recipients and is a major early complication. Preventive strategies, ECMO support, and infection management are critical. Attention to airway complications and acute kidney injury further improves recovery.
- Immunosuppression: Maintenance therapy typically includes a calcineurin inhibitor, glucocorticoid, and cell-cycle inhibitor. Induction therapy is individualized. Ongoing studies are exploring adjunct therapies like mTOR inhibitors and inhaled immunosuppressants to prevent CLAD.
- Management of ALAD and CLAD: Early detection and treatment of acute lung allograft dysfunction are essential. CLAD, affecting half of recipients within 5 years, remains a major challenge. Current therapies slow progression, but further research is needed for targeted prevention and treatment.
- Infections: Infections remain a leading cause of morbidity and mortality. Prophylaxis against cytomegalovirus, fungal pathogens, and community-acquired viruses is essential to minimize complications and reduce CLAD risk.
- Cancer Risk: Post-transplant cancer risk is elevated due to immunosuppression. Lung cancer and post-transplant lymphoproliferative disease are the most common malignancies, emphasizing the need for routine surveillance and early intervention.
- Long-Term Outcomes: Median survival remains limited at 6.7 years. Efforts focus on improving long-term outcomes by balancing graft function maintenance with minimizing adverse effects of immunosuppression. Collaborative research aims to refine diagnostics, personalize therapies, and address CLAD mechanisms.
Conclusion: Enhanced donor utilization, tailored candidate selection, refined perioperative care, and robust long-term monitoring are pivotal to advancing lung transplantation. Ongoing research and collaboration are critical to overcoming challenges like CLAD, improving survival, and enhancing patient quality of life.
News Release: Seven-Day Antibiotic Regimen Effective for Bloodstream Infections
10 Nov, 2024 | 17:54h | UTCIntroduction: A recent large-scale, multicenter randomized clinical trial has shown that a seven-day course of antibiotics is as effective as the traditional 14-day regimen for treating hospitalized patients with bloodstream infections (BSIs). This finding addresses a critical need in medical practice to optimize antibiotic use amid rising concerns about antimicrobial resistance and healthcare costs.
Highlights: The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial evaluated 3,608 patients with BSIs across 74 hospitals in seven countries, including the United States, Canada, and Australia. Patients were randomized to receive either a seven-day or a 14-day antibiotic course, with the choice of antibiotic, dosage, and administration route determined by their healthcare team.
- Efficacy Results: The 90-day mortality rates were similar between the two groups—14.5% in the seven-day group versus 16.1% in the 14-day group—demonstrating the non-inferiority of the shorter regimen.
- Secondary Outcomes: Rates of relapse, ICU mortality, hospital mortality, and other clinical markers showed no significant differences between the two groups.
- Patient Demographics: The study included a diverse patient population, with 55% in intensive care units at enrollment. Infections originated from various sources, most commonly the urinary tract (42.2%), abdomen (18.8%), and lungs (13.0%).
- Applicability: Exclusion criteria were minimal, enhancing the generalizability of the findings to everyday clinical practice. Patients with extreme immunosuppression or undrained abscesses were excluded, but those with conditions like renal failure were included.
Lead investigator Dr. Nick Daneman emphasized, “These findings underscore the effectiveness of a shorter antibiotic regimen in patients with bloodstream infections, which is welcomed as we look to identify evidence-based prescribing guidelines for serious bacterial infections.”
Conclusion: The BALANCE trial provides robust evidence that a seven-day antibiotic course is sufficient for treating BSIs, potentially transforming current clinical practice. Adopting shorter antibiotic regimens can reduce healthcare costs, minimize adverse effects, and combat antimicrobial resistance without compromising patient outcomes. This aligns with antimicrobial stewardship goals and promotes more efficient use of healthcare resources.
Source: This study was presented at IDWeek 2024, the joint annual meeting of the Infectious Diseases Society of America and other related organizations. The research was conducted by a team from Sunnybrook Health Sciences Centre and the University of Toronto, led by Dr. Nick Daneman and Dr. Robert Fowler. More information can be found at: http://www.idsociety.org/news–publications-new/articles/2024/antibiotic-treatment-regimen-for-bloodstream-infections-can-safely-be-cut-by-half
Guideline: Management of Urinary Tract Infections in Pediatrics and Adults
5 Nov, 2024 | 18:59h | UTCIntroduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.
Key Recommendations:
- Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
- Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
- Nitrofurantoin: 5 days
- Trimethoprim/sulfamethoxazole: 3 days
- Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
- Fluoroquinolones: 5–7 days
- Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong
Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.
Observational Study: Kidney Transplantation from Donors with HIV Safe for Recipients with HIV
20 Oct, 2024 | 17:30h | UTCBackground: Kidney transplantation improves survival for persons with HIV and end-stage renal disease but is limited by organ shortages. Transplantation from donors with HIV to recipients with HIV is emerging under the HIV Organ Policy Equity (HOPE) Act but is currently approved only for research. The Department of Health and Human Services is considering expanding this practice to clinical care, but data are limited to small case series without control groups.
Objective: To assess whether kidney transplantation from donors with HIV is noninferior to transplantation from donors without HIV regarding safety outcomes in recipients with HIV.
Methods: In an observational, noninferiority study at 26 U.S. centers, 408 transplantation candidates with HIV were enrolled. Of these, 198 received a kidney transplant: 99 from deceased donors with HIV and 99 from deceased donors without HIV. The primary outcome was a composite safety event (death, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (upper bound of 95% CI for hazard ratio ≤3.00). Secondary outcomes included overall survival, survival without graft loss, rejection rates, infections, cancer, and HIV superinfection.
Results: The adjusted hazard ratio for the composite primary outcome was 1.00 (95% CI, 0.73 to 1.38), demonstrating noninferiority. Overall survival at 1 year was 94% for recipients of kidneys from donors with HIV and 95% for those from donors without HIV; at 3 years, survival was 85% and 87%, respectively. Survival without graft loss at 1 year was 93% vs. 90%; at 3 years, 84% vs. 81%. Rejection rates were similar at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer did not differ significantly between groups. HIV breakthrough infection occurred more frequently among recipients of kidneys from donors with HIV (incidence rate ratio 3.14; 95% CI, 1.02 to 9.63), primarily due to nonadherence to antiretroviral therapy; viral suppression was regained in all cases. One potential HIV superinfection occurred without clinical consequences.
Conclusions: Kidney transplantation from donors with HIV to recipients with HIV was noninferior to transplantation from donors without HIV regarding safety outcomes, supporting the expansion of this practice from research to clinical care.
Implications for Practice: Expanding kidney transplantation involving donors and recipients with HIV to clinical practice could increase organ availability and reduce disparities in transplantation access for persons with HIV. Clinicians should monitor for HIV breakthrough infections and encourage adherence to antiretroviral therapy.
Study Strengths and Limitations: Strengths include a multicenter design and direct comparison groups. Limitations involve the observational design, inability to randomize due to allocation constraints, and heterogeneity in immunosuppression protocols.
Future Research: Further studies are needed to confirm these findings, evaluate long-term outcomes, and assess potential risks such as HIV superinfection.
Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines
12 Oct, 2024 | 18:23h | UTCIntroduction: Ascites, the pathological accumulation of fluid within the peritoneal cavity, is a common and serious complication of cirrhosis, indicating advanced liver disease and portending increased morbidity and mortality. Recognizing the need for updated clinical guidance, the British Society of Gastroenterology (BSG), in collaboration with the British Association for the Study of the Liver (BASL), has issued comprehensive guidelines. These aim to standardize the diagnosis and management of ascites in cirrhotic patients, incorporating recent advances to optimize patient outcomes.
Key Recommendations:
- Diagnostic Paracentesis: It is strongly recommended that all patients with new-onset ascites undergo diagnostic paracentesis to measure total protein concentration and calculate the serum-ascites albumin gradient (SAAG). (Quality of evidence: moderate; Recommendation: strong)
- Spontaneous Bacterial Peritonitis (SBP): Prompt diagnostic paracentesis should be performed in hospitalized patients with ascites, especially those with gastrointestinal bleeding or signs of infection, to rule out SBP. An ascitic neutrophil count >250/mm³ confirms SBP, necessitating immediate empirical antibiotic therapy tailored to local resistance patterns. (Quality of evidence: moderate; Recommendation: strong)
- Dietary Salt Restriction: Patients should restrict dietary sodium intake to no more than 5–6.5 grams per day (87–113 mmol), equivalent to a no-added-salt diet, to manage fluid accumulation effectively. (Quality of evidence: moderate; Recommendation: strong)
- Diuretic Therapy: For initial moderate ascites, spironolactone monotherapy is recommended. In cases of recurrent severe ascites, combination therapy with spironolactone and furosemide is advised. Regular monitoring for adverse events such as electrolyte imbalances and renal impairment is essential. (Quality of evidence: moderate; Recommendation: strong)
- Large Volume Paracentesis (LVP): LVP is a safe and effective treatment for refractory ascites. Informed consent is required, and routine coagulation studies or prophylactic blood product infusions before the procedure are not recommended. (Quality of evidence: moderate; Recommendation: strong)
- Use of Human Albumin Solution (HAS): After LVP exceeding 5 liters, infusion of HAS at 8 grams per liter of ascites removed is strongly recommended to prevent circulatory dysfunction. (Quality of evidence: high; Recommendation: strong)
- Transjugular Intrahepatic Portosystemic Shunt (TIPSS): TIPSS should be considered for patients with refractory ascites not responding to medical therapy, with caution exercised in patients over 70 years or those with significant comorbidities. (Quality of evidence: high; Recommendation: strong)
- Non-Selective Beta-Blockers (NSBBs): The presence of refractory ascites is not a contraindication for NSBB therapy. Patients should be closely monitored, and dose adjustments made in cases of hypotension or renal dysfunction. (Quality of evidence: moderate; Recommendation: strong)
- Palliative Care: Patients unsuitable for liver transplantation should be offered palliative care referral to focus on symptom management and quality of life improvement. Alternative interventions for refractory ascites may also be considered. (Quality of evidence: weak; Recommendation: strong)
Conclusion: Implementation of these evidence-based guidelines is expected to enhance patient care by promoting early diagnosis, preventing complications, and standardizing management strategies for ascites in cirrhosis. Adherence to these recommendations can improve clinical outcomes, reduce hospitalizations, and enhance the quality of life for affected patients.
Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD
6 Oct, 2024 | 17:12h | UTCBackground: Respiratory tract infections (RTIs) significantly contribute to global disease burden and antibiotic usage. Optimizing antibiotic treatment duration is crucial for antimicrobial stewardship to minimize resistance. Despite evidence supporting shorter antibiotic courses for RTIs, prolonged treatment durations persist in clinical practice.
Objective: To evaluate the current evidence base for optimal antibiotic treatment durations in RTIs and determine whether shorter courses are supported.
Methods: An umbrella review was conducted by searching Ovid MEDLINE, Embase, and Web of Science up to May 1, 2024, without language restrictions. Systematic reviews comparing antibiotic treatment durations for community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis in adults were included. Pediatric-focused reviews were excluded. Quality assessments utilized the AMSTAR 2 tool for reviews and the Cochrane risk-of-bias tool (version 1) for randomized controlled trials (RCTs). The GRADE approach determined the overall quality of evidence.
Results: Thirty systematic reviews were included, generally of low to critically low quality. For non-ICU CAP (14 reviews), moderate-quality evidence supports a 5-day antibiotic course, with insufficient data for shorter durations. In AECOPD (eight reviews), a 5-day treatment was non-inferior to longer courses regarding clinical and microbiological cure, with similar or fewer adverse events. Evidence for non-ventilator-associated HAP is lacking. In acute sinusitis, shorter regimens appear effective, but further research is needed for patients requiring antibiotics. For pharyngotonsillitis (eight reviews), evidence supports short-course cephalosporin therapy but not short-course penicillin when dosed three times daily.
Conclusions: Evidence supports a 5-day antibiotic treatment duration for non-ICU CAP and AECOPD in clinically improving patients. Implementing this evidence in practice is essential. High-quality RCTs are needed to assess shorter durations for CAP and AECOPD, establish optimal durations for HAP and acute sinusitis, and evaluate short-course penicillin with optimal dosing in pharyngotonsillitis.
Implications for Practice: Clinicians should adopt 5-day antibiotic courses for non-ICU CAP and AECOPD in patients showing clinical improvement, aligning with antimicrobial stewardship objectives to reduce unnecessary antibiotic exposure and resistance development.
Study Strengths and Limitations: Strengths include a comprehensive search and assessment of systematic reviews and meta-analyses. Limitations involve the generally low quality of included reviews and RCTs, with many studies exhibiting unclear or high risk of bias. Heterogeneity in definitions of short-course treatment and variability in patient populations and settings were also noted.
Future Research: High-quality RCTs are required to investigate antibiotic durations shorter than 5 days for CAP and AECOPD, determine optimal treatment lengths for HAP and acute sinusitis, and assess short-course penicillin therapy with optimal dosing schedules in pharyngotonsillitis.
RCT: H. pylori Screening Added to Fecal Immunochemical Testing Did Not Reduce Gastric Cancer Incidence or Mortality
4 Oct, 2024 | 11:00h | UTCBackground: Gastric cancer is a leading cause of cancer-related mortality worldwide, particularly in East Asia. Helicobacter pylori infection is a well-established risk factor for gastric cancer development. While eradication therapy may prevent gastric cancer, the effectiveness of community-based H. pylori screening on gastric cancer incidence and mortality remains uncertain.
Objective: To determine whether adding H. pylori stool antigen (HPSA) testing to fecal immunochemical test (FIT) screening reduces gastric cancer incidence and mortality compared to FIT screening alone.
Methods: In a pragmatic randomized clinical trial conducted in Changhua County, Taiwan (2014–2018), 152,503 residents aged 50 to 69 years eligible for biennial FIT screening were randomized to receive an invitation for HPSA testing plus FIT (n = 63,508) or FIT alone (n = 88,995). Participants in the HPSA + FIT group with positive HPSA results were offered antibiotic eradication therapy. Primary outcomes were gastric cancer incidence and mortality, assessed via national cancer and death registries.
Results: Participation rates were higher in the HPSA + FIT group (49.6%) than in the FIT-alone group (35.7%). In the HPSA + FIT group, 38.5% tested positive for HPSA, and 71.4% of these received antibiotic treatment, achieving a 91.9% eradication rate. Over a median follow-up of approximately 5 years, gastric cancer incidence did not differ significantly between the HPSA + FIT and FIT-alone groups (0.032% vs 0.037%; mean difference –0.005%; 95% CI, –0.013% to 0.003%; P = .23). Gastric cancer mortality rates were also similar (0.015% vs 0.013%; mean difference 0.002%; 95% CI, –0.004% to 0.007%; P = .57). Adjusted analyses accounting for participation rates, follow-up duration, and baseline characteristics showed a lower gastric cancer incidence in the HPSA + FIT group (RR 0.79; 95% CI, 0.63–0.98; P = .04), but no difference in mortality (RR 1.02; 95% CI, 0.73–1.40; P = .91). Adverse effects from antibiotics were mild, with abdominal pain or diarrhea occurring in 2.1%.
Conclusions: An invitation to HPSA testing combined with FIT did not significantly reduce gastric cancer incidence or mortality compared to FIT alone over a median follow-up of about 5 years. Adjusted analyses suggest a potential reduction in gastric cancer incidence but not mortality when accounting for participation rates and follow-up duration.
Implications for Practice: Adding H. pylori screening to existing FIT programs may not significantly reduce gastric cancer incidence or mortality in the short term, possibly due to low participation rates, incomplete eradication, and limited follow-up. Clinicians should consider these factors when implementing community-based H. pylori screening and weigh the benefits against resource utilization and patient adherence.
Study Strengths and Limitations: Strengths include a large sample size and integration of HPSA testing into an existing FIT screening infrastructure. Limitations encompass differences in participation rates and baseline characteristics between groups, a relatively short follow-up period, and only 71.4% of HPSA-positive participants receiving eradication therapy, which may have reduced the ability to detect significant effects.
Future Research: Longer-term studies with higher participation and eradication rates are needed to assess the long-term benefits of H. pylori screening on gastric cancer incidence and mortality. Research should explore strategies to improve screening uptake and treatment adherence.
Summary: Community-Acquired Pneumonia
19 Sep, 2024 | 17:21h | UTCIntroduction
Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, accounting for approximately 1.4 million emergency department visits, 740,000 hospitalizations, and 41,000 deaths annually in the United States. Effective management of CAP requires prompt and accurate diagnosis, appropriate antimicrobial therapy, and consideration of adjunctive treatments. This summary highlights key practice points from a review article in JAMA related to the diagnosis and treatment of CAP for medical professionals.
Diagnosis of CAP
Clinical Presentation
- Signs and Symptoms: Suspect CAP in patients presenting with two or more of the following:
- Fever (>38 °C) or hypothermia (≤36 °C)
- Leukocytosis (>10,000/μL) or leukopenia (<4,000/μL)
- New or increased cough
- Dyspnea
Radiographic Confirmation
- Chest Imaging: Obtain a chest radiograph for all patients with suspected CAP to identify air space opacities or infiltrates.
- Chest CT: Consider if the chest radiograph is inconclusive but clinical suspicion remains high.
- Differential Diagnosis: Rule out other causes of symptoms and radiographic findings, such as pulmonary embolism, heart failure, or malignancy.
Microbiological Testing
- Viral Testing:
- SARS-CoV-2 and Influenza: Test all patients for COVID-19 and influenza during periods of community transmission, as results influence treatment decisions and infection control measures.
- Bacterial Testing:
- Indications: Reserve sputum and blood cultures for patients with severe CAP or risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
- Risk Factors:
- Previous infection or colonization with MRSA or P. aeruginosa.
- Hospitalization with parenteral antibiotics within the past 90 days.
Treatment of CAP
Empirical Antimicrobial Therapy
- Hospitalized Patients without Risk Factors for Resistant Bacteria:
- First-Line Therapy: β-lactam plus macrolide combination.
- Example: Ceftriaxone (1-2 g IV daily) plus azithromycin (500 mg IV or orally daily).
- Alternative: Respiratory fluoroquinolone monotherapy (e.g., levofloxacin) if β-lactam/macrolide therapy is contraindicated.
- First-Line Therapy: β-lactam plus macrolide combination.
- Patients with Severe CAP:
- Similar to non-severe CAP but ensure coverage for atypical pathogens.
- Consider Corticosteroids: Early administration (within 24 hours) of systemic corticosteroids may reduce mortality.
- Outpatients without Comorbidities:
- First-Line Therapy: Amoxicillin (1 g orally three times daily) or doxycycline (100 mg orally twice daily).
- Outpatients with Comorbidities:
- Combination Therapy: Amoxicillin/clavulanate (500 mg/125 mg orally three times daily) plus azithromycin (500 mg on day 1, then 250 mg daily).
Duration of Therapy
- Minimum Duration: Treat for a minimum of 3 days if the patient achieves clinical stability (normal vital signs) within 72 hours.
- Extended Duration: Extend to 5 days or more if the patient does not meet stability criteria by day 3 or has complications.
- Transition to Oral Therapy: Switch from intravenous to oral antibiotics when the patient can tolerate oral intake.
Antimicrobial Stewardship
- Avoid Unnecessary Antibiotics: Do not initiate antibiotics for confirmed viral CAP without evidence of bacterial coinfection.
- De-escalation: Narrow antibiotic coverage based on culture results and clinical improvement.
- Monitor for Adverse Effects: Be vigilant for antibiotic-associated complications, such as Clostridioides difficile infection.
Adjunctive Therapies
- Corticosteroids:
- Severe CAP: Administer systemic corticosteroids (e.g., hydrocortisone 200 mg/day) within 24 hours of diagnosis to reduce mortality and complications.
- Non-severe CAP: Routine use is not recommended due to lack of benefit and potential harm.
Secondary Prevention
- Vaccinations:
- Pneumococcal Conjugate Vaccine: Recommend for eligible patients to prevent future pneumococcal infections.
- Influenza Vaccine: Annual vaccination to reduce the risk of influenza-associated pneumonia.
- COVID-19 and RSV Vaccines: Encourage vaccination per current guidelines.
- Lifestyle Modifications:
- Smoking Cessation: Strongly advise quitting smoking to reduce the risk of CAP and improve respiratory health.
- Alcohol Moderation: Counsel patients on reducing excessive alcohol intake.
- Management of Comorbidities:
- Optimize treatment for chronic conditions such as chronic obstructive pulmonary disease (COPD), heart failure, and diabetes.
Key Practice Points
- Diagnostic Evaluation:
- Use a combination of clinical signs, symptoms, and radiographic findings to diagnose CAP.
- Test all patients for SARS-CoV-2 and influenza during times of community prevalence.
- Reserve extensive pathogen testing for severe cases or those at risk for resistant organisms.
- Antimicrobial Therapy:
- Initiate empirical antibiotics promptly based on disease severity and risk factors.
- Prefer β-lactam/macrolide combination therapy for most hospitalized patients.
- Limit the duration of antibiotics to the shortest effective course to reduce resistance and adverse effects.
- Use of Corticosteroids:
- Consider early corticosteroid therapy in patients with severe CAP to improve outcomes.
- Avoid routine corticosteroid use in non-severe CAP due to potential risks.
- Antimicrobial Stewardship:
- Reassess antibiotic therapy daily and de-escalate based on clinical response and microbiological data.
- Transition to oral antibiotics when appropriate.
- Preventive Measures:
- Promote vaccinations and lifestyle changes to prevent recurrent CAP.
- Address and manage underlying health conditions that may predispose to CAP.
Conclusion
Effective management of CAP involves prompt diagnosis using clinical and radiographic criteria, appropriate empirical antimicrobial therapy tailored to disease severity and risk factors, and consideration of adjunctive treatments such as corticosteroids in severe cases. Antimicrobial stewardship principles should guide therapy duration and de-escalation to minimize resistance and adverse effects. Preventive strategies, including vaccinations and lifestyle modifications, are essential to reduce the incidence of CAP and improve patient outcomes.
Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies
7 Sep, 2024 | 20:36h | UTCStudy Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.
Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.
Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.
Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380
Link: https://jamanetwork.com/journals/jama/fullarticle/2822933
Cluster-Randomized Trial: Twice-Yearly Azithromycin Reduces Mortality in Children Aged 1 to 59 Months in Niger – New England Journal of Medicine
24 Aug, 2024 | 19:44h | UTCStudy Design and Population: This adaptive cluster-randomized trial evaluated the impact of twice-yearly azithromycin distribution on childhood mortality in rural communities in Niger. A total of 1273 communities were assigned to three groups: children aged 1 to 59 months receiving azithromycin, infants aged 1 to 11 months receiving azithromycin and placebo for older children, and a placebo group. The study included 382,586 children and followed mortality over 419,440 person-years.
Main Findings: The study found a significant 14% reduction in mortality among children aged 1 to 59 months in the azithromycin group compared to placebo (11.9 vs. 13.9 deaths per 1000 person-years; P<0.001). However, azithromycin did not significantly reduce mortality in infants aged 1 to 11 months when compared to placebo (22.3 vs. 23.9 deaths per 1000 person-years).
Implications for Practice: Azithromycin distribution to children aged 1 to 59 months effectively reduces mortality in rural sub-Saharan Africa. However, targeting only infants may not yield significant benefits. Continuous monitoring for antimicrobial resistance is essential.
Innovative Antimicrobial Susceptibility Testing Bypasses Blood Culture, Promising Faster Sepsis Diagnosis – Nature
18 Aug, 2024 | 14:09h | UTCStudy Design and Population: This study introduces a novel ultra-rapid antimicrobial susceptibility testing (AST) method that bypasses the traditional blood culture process, potentially reducing diagnostic time by 40-60 hours. The method was evaluated using a cohort of 190 hospitalized patients in Korea with suspected sepsis, including those with blood cancers.
Main Findings: The new AST method identified bacterial species in all patients with positive blood infections, achieving a 100% match in species identification. For antimicrobial susceptibility, the method demonstrated a 94.9% categorical agreement with conventional AST methods, with a theoretical turnaround time of 13 ± 2.53 hours, significantly faster than current workflows.
Implications for Practice: This method could improve sepsis treatment by providing same-day results, potentially reducing sepsis-related mortality and the use of broad-spectrum antibiotics. However, further validation in a more diverse patient population is necessary to confirm its clinical efficacy and value.
RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med
18 Aug, 2024 | 13:56h | UTCStudy Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.
Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.
Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.
Review: Prevention and Management of Device-Associated Complications in the Intensive Care Unit – The BMJ
17 Aug, 2024 | 20:04h | UTCIntroduction:
This review article, published by experts from the David Geffen School of Medicine at UCLA, focuses on the complications associated with invasive devices commonly used in the Intensive Care Unit (ICU). While these devices are essential for managing critically ill patients, they also pose significant risks, necessitating a thorough understanding of their potential complications and strategies for prevention and management.
Key Points:
1 – Central Venous Catheters (CVCs):
– CVCs are widely used in ICU patients but carry risks like vascular injury, pneumothorax, thrombosis, and infection.
– Use of real-time ultrasound guidance and careful operator technique are crucial for minimizing these risks.
– Prompt removal of unnecessary CVCs is essential to reduce the risk of complications.
2 – Arterial Catheters:
– Commonly used for hemodynamic monitoring, these catheters can lead to complications such as vascular occlusion, nerve injury, and infection.
– Ultrasound guidance is recommended to reduce the risk of complications, and catheters should be discontinued as soon as clinically feasible.
3 – Airway Devices (Endotracheal Tubes and Tracheostomies):
– Complications include laryngeal injury, tracheal stenosis, and tracheomalacia.
– Strategies to reduce these risks include minimizing intubation attempts, ensuring proper tube placement, and managing cuff pressures carefully.
4 – Extracorporeal Membrane Oxygenation (ECMO):
– ECMO is associated with significant complications, including bleeding, thromboembolic events, and neurologic injuries.
– Proper cannulation technique and vigilant monitoring are essential to mitigate these risks.
5 – Infection Control:
– Strict adherence to aseptic techniques and the use of chlorhexidine-impregnated dressings are recommended to prevent device-associated infections.
Conclusion:
This review underscores the importance of judicious use and timely removal of invasive devices in the ICU to minimize complications. Healthcare professionals must remain vigilant and employ best practices to prevent and manage these complications effectively.
Meta-Analysis: Inhaled Antibiotics Offer Modest Reductions in Exacerbations and Quality of Life Gains in Bronchiectasis – CHEST
11 Aug, 2024 | 13:12h | UTCStudy Design and Population: This study is an updated systematic review and meta-analysis of 20 randomized controlled trials involving 3,468 adults with bronchiectasis, who were treated with inhaled antibiotics. The trials included in the analysis were selected based on criteria such as a minimum treatment duration of 4 weeks and involved patients diagnosed by CT imaging. The primary endpoint was exacerbation frequency, while secondary endpoints included severe exacerbations, bacterial load, symptoms, quality of life, and FEV1.
Main Findings: The meta-analysis found that inhaled antibiotics modestly reduced the proportion of patients experiencing exacerbations (risk ratio [RR], 0.85) and exacerbation frequency (RR, 0.78). Severe exacerbations were also decreased (RR, 0.48), and there was a slight increase in the time to the first exacerbation (hazard ratio [HR], 0.80). Additionally, quality of life showed modest improvements as measured by the Quality of Life Questionnaire-Bronchiectasis (mean difference, 2.51) and the St. George Respiratory Questionnaire (mean difference, -3.13). Bacterial load was consistently reduced, although FEV1 did not change meaningfully with treatment. The rate of adverse effects was similar to placebo (odds ratio [OR], 0.99), but antibiotic resistance appeared more likely to increase with treatment.
Implications for Practice: Inhaled antibiotics appear to be a beneficial treatment for adults with bronchiectasis, as they can reduce both exacerbation rates and severity while also improving quality of life. However, the increased risk of antibiotic resistance is a concern, indicating the need for careful patient selection and monitoring during treatment. These findings support the use of inhaled antibiotics in appropriate cases, particularly for those at high risk of exacerbations.
IDSA 2024 Guidelines for Managing Complicated Intra-abdominal Infections – Clin Infect Dis
10 Aug, 2024 | 22:10h | UTCIntroduction: The Infectious Diseases Society of America (IDSA) has updated its clinical practice guidelines for managing complicated intra-abdominal infections in adults, children, and pregnant individuals. The update focuses on risk assessment, diagnostic imaging, and microbiological evaluation, with recommendations grounded in systematic literature reviews and the GRADE approach for rating evidence.
Key Points:
1 – Risk Stratification:
– For adults with complicated intra-abdominal infections, the APACHE II score is recommended for risk stratification within 24 hours of hospital or ICU admission. The WSES Sepsis Severity Score is an acceptable alternative.
– No specific severity scoring system is recommended for pediatric patients.
2 – Diagnostic Imaging for Appendicitis:
– In non-pregnant adults, CT is suggested as the initial imaging modality for suspected acute appendicitis.
– For children, an abdominal ultrasound (US) is preferred initially, with MRI or CT recommended if the US is inconclusive.
– In pregnant individuals, US or MRI can be considered, with MRI suggested if initial US results are inconclusive.
3 – Imaging for Acute Cholecystitis and Cholangitis:
– For non-pregnant adults, US is recommended initially. If inconclusive, a CT scan is suggested.
– For pregnant individuals, US or MRI can be used, but the guidelines do not specify a preferred modality due to a knowledge gap.
4 – Blood Cultures:
– Blood cultures are recommended in adults and children with suspected intra-abdominal infections presenting with severe symptoms such as hypotension or tachypnea, especially when antibiotic-resistant organisms are a concern.
– Routine blood cultures are not recommended for patients without these risk factors.
5 – Intra-abdominal Fluid Cultures:
– In complicated intra-abdominal infections requiring source control procedures, obtaining intra-abdominal cultures is advised to guide antimicrobial therapy.
– In uncomplicated appendicitis cases, routine cultures are not recommended unless the patient is immunocompromised or complicated disease is suspected during surgery.
Conclusion: These guidelines provide evidence-based recommendations to improve the management of complicated intra-abdominal infections, emphasizing appropriate risk stratification, targeted diagnostic imaging, and the selective use of cultures to guide therapy.
Nested Case-Control Study: Sulfonamide Antibiotics and Cephalosporins Linked to Highest Risk of Serious Cutaneous Adverse Drug Reactions – JAMA
10 Aug, 2024 | 21:16h | UTCStudy Design and Population: This population-based, nested case-control study assessed the risk of serious cutaneous adverse drug reactions (cADRs) among older adults (66 years and above) in Ontario, Canada, who received oral antibiotics between 2002 and 2022. The study included 21,758 cases of emergency department visits or hospitalizations for serious cADRs, matched with 87,025 controls.
Main Findings: The study found that sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9) and cephalosporins (aOR, 2.6) posed the highest risk of serious cADRs compared to macrolides. Nitrofurantoin, penicillins, and fluoroquinolones also showed elevated risks. Cephalosporins had the highest crude rate of cADRs (4.92 per 1,000 prescriptions).
Implications for Practice: The findings suggest that clinicians should consider the higher risks of serious cADRs associated with sulfonamide antibiotics and cephalosporins when prescribing antibiotics, opting for lower-risk alternatives when appropriate.
Phase 3 RCT: Butantan-DV Dengue Vaccine is Safe and Shows 67.3% Efficacy Over 3.7 Years in Participants Aged 2–59 Years – Lancet Infect Dis
10 Aug, 2024 | 20:23h | UTCStudy Design and Population: This double-blind, randomized, placebo-controlled, phase 3 trial conducted in Brazil evaluated the efficacy and safety of the Butantan-dengue vaccine (Butantan-DV) in 16,235 healthy participants aged 2–59 years. Participants, who had not previously received a dengue vaccine, were randomly assigned to receive either a single dose of Butantan-DV or a placebo and were followed up for an average of 3.7 years.
Main Findings: The study found that Butantan-DV demonstrated 67.3% efficacy against virologically confirmed dengue (VCD) caused by any dengue virus serotype, with no cases of VCD caused by DENV-3 or DENV-4. The proportions of serious adverse events were similar between the vaccine and placebo groups, indicating that the vaccine was generally well tolerated.
Implications for Practice: The results support the potential of the Butantan-DV vaccine as an effective intervention for preventing symptomatic dengue, particularly from DENV-1 and DENV-2, across a broad age range regardless of dengue serostatus. Continued development and monitoring are warranted to confirm long-term efficacy and safety.
IDSA 2024 Guidelines for Treatment of Antimicrobial-Resistant Gram-Negative Infections – Clin Infect Dis
10 Aug, 2024 | 20:16h | UTCIntroduction:
The Infectious Diseases Society of America (IDSA) has released updated guidelines in 2024 addressing the treatment of infections caused by antimicrobial-resistant (AMR) Gram-negative bacteria. These guidelines cover pathogens including extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia.
Key Points:
1 – ESBL-E Infections:
– Preferred treatment for uncomplicated cystitis includes nitrofurantoin and TMP-SMX. Fluoroquinolones and carbapenems are alternatives but should be reserved to prevent resistance.
– For pyelonephritis or complicated urinary tract infections (cUTI), TMP-SMX, ciprofloxacin, or levofloxacin are preferred. Carbapenems are recommended when resistance precludes other options.
2 – AmpC-E Infections:
– Cefepime is suggested for treating infections caused by organisms at moderate risk of significant AmpC production (e.g., Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii).
– The use of cephamycins (e.g., cefoxitin, cefotetan) for treating ESBL-E infections is not recommended due to insufficient clinical outcome data.
3 – CRE Infections:
– Acknowledgement of increased prevalence of metallo-beta-lactamase (MBL)-producing CRE in the U.S.
– The combination of ceftazidime-avibactam and aztreonam is suggested for MBL-producing CRE, with updated dosing recommendations provided.
4 – DTR Pseudomonas aeruginosa:
– Traditional β-lactams (e.g., cefepime) with high-dose extended-infusion therapy are recommended.
– Tobramycin or amikacin, administered once daily, are alternatives for pyelonephritis or cUTI.
5 – CRAB and Stenotrophomonas maltophilia Infections:
– Sulbactam-durlobactam with meropenem or imipenem-cilastatin is the preferred treatment for CRAB.
– The order of preference for agents treating S. maltophilia includes cefiderocol, ceftazidime-avibactam, and aztreonam, among others.
Conclusion:
The 2024 IDSA guidelines provide critical updates on managing AMR Gram-negative infections, emphasizing the importance of selecting the appropriate antibiotic based on susceptibility, resistance mechanisms, and patient-specific factors. These guidelines are essential for optimizing treatment outcomes in the face of increasing antimicrobial resistance.
Reference: