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Antibiotic Stewardship

Multidrug-resistant Gram-negative bacterial infections: Key Updates and Practical Strategies

25 Jan, 2025 | 22:53h | UTC

Introduction: This summary highlights essential points from a recent review in The Lancet addressing multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. It discusses the global epidemiology, diagnostic advances, and therapeutic approaches, aiming to guide clinicians in managing these difficult-to-treat pathogens, which include resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Key Recommendations:

  1. Use Rapid Diagnostics to Guide Therapy
    • Employ molecular tests (e.g., multiplex PCR) to detect resistance genes quickly and facilitate targeted treatment.
    • Consider phenotypic assays (e.g., CarbaNP, carbapenemase inactivation method) and MALDI-TOF for rapid organism identification and mechanism-specific information.
  2. Optimize Antibiotic Selection Based on Resistance Mechanisms
    • AmpC-Producing Enterobacterales (e.g., Enterobacter spp.): Use cefepime if in vitro susceptibility is confirmed.
    • ESBL-Producing Enterobacterales: Carbapenems (e.g., meropenem) remain the mainstay for serious infections.
    • Carbapenem-Resistant Enterobacterales (CRE): Use novel β-lactam/β-lactamase inhibitor agents (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam) based on specific carbapenemase mechanisms. For metallo-β-lactamase producers, consider aztreonam plus ceftazidime–avibactam or future co-formulations (e.g., aztreonam–avibactam).
    • DTR-Pseudomonas aeruginosa: Ceftolozane–tazobactam is preferred if active in vitro. Ceftazidime–avibactam or imipenem–relebactam may also be options depending on local susceptibility data.
    • Carbapenem-Resistant Acinetobacter baumannii (CRAB): High-dose sulbactam combinations (e.g., sulbactam–durlobactam) were studied in combination with imipenem–cilastatin during trials; further data are needed to clarify optimal clinical use.
  3. Consider Non-Antibiotic Modalities for Refractory Cases
    • Investigational therapies—such as bacteriophages and antivirulence agents—are under clinical evaluation.
    • Fecal microbiota transplantation has shown variable decolonization efficacy in small studies, and randomized trials have yielded limited or inconclusive results.
  4. Emphasize Antimicrobial Stewardship and Infection Control
    • Restrict newer agents to cases where standard treatments have failed or resistance patterns require them.
    • Maintain rigorous infection control practices (e.g., contact precautions, hand hygiene, isolation measures) to reduce nosocomial spread of MDR-GNB.
    • Observational data suggest shorter antibiotic courses (7–10 days) might be adequate in select cases, but robust clinical trial evidence is still pending.

Conclusion:
By combining rapid diagnostics, judicious use of existing and novel antibiotics, and robust infection prevention measures, clinicians can significantly improve outcomes for patients with MDR-GNB infections. However, access to advanced diagnostics and new therapies remains limited in many regions, and further clinical trials are needed to determine optimal treatment and duration strategies. Early mechanism-focused detection and targeted therapy enhance clinical success, reduce toxicity, and help preserve the efficacy of newly approved agents.

Reference:
Macesic N, Uhlemann A-C, Peleg AY. Multidrug-resistant Gram-negative bacterial infections. The Lancet. 2025;405(10474):257-272. DOI: https://doi.org/10.1016/S0140-6736(24)02081-6

 

RCT: Albendazole–Ivermectin Co-Formulation Achieves Higher Cure Rates for T. trichiura and Hookworms

22 Jan, 2025 | 12:41h | UTC

Background: Soil-transmitted helminthiases (STH) affect an estimated 1.5 billion people worldwide, with Trichuris trichiura and hookworms remaining particularly challenging to treat. Although single-dose albendazole or mebendazole is standard in mass deworming programs, these agents show limited efficacy against T. trichiura and often leave Strongyloides stercoralis under-treated. Ivermectin has demonstrated broad activity against multiple parasites, suggesting that a combined albendazole–ivermectin regimen might enhance treatment outcomes, simplify protocols, and potentially curb emerging drug resistance.

Objective: This trial aimed to evaluate the safety, efficacy, and acceptability of a novel fixed-dose co-formulation (FDC) tablet containing albendazole (400 mg) plus a higher-than-standard, fixed dose of ivermectin (9 mg or 18 mg), administered once daily (FDC×1) or for three consecutive days (FDC×3). Investigators compared these regimens against single-dose albendazole alone for the treatment of T. trichiura, hookworms, and S. stercoralis in children and adolescents.

Methods: In this adaptive, randomized, parallel-group, phase 2/3 trial, 1001 participants aged 5–18 years were recruited from schools in Ethiopia, Kenya, and Mozambique. All were infected with at least one of T. trichiura, hookworms, or S. stercoralis. Eligible participants were allocated (by computer-generated block randomization) to either a single dose of albendazole 400 mg (control), a single-dose FDC of albendazole–ivermectin (FDC×1), or a three-day FDC regimen (FDC×3). Primary endpoints included safety (phase 2) and efficacy (phase 3), determined by cure rates at day 21 using the Kato–Katz and Baermann methods. Laboratory staff were blinded to treatment assignment.

Results: No serious adverse events were reported; mild-to-moderate gastrointestinal symptoms were the most frequent treatment-related events, resolving spontaneously within 48 hours. Cure rates for T. trichiura were 35.9% (95% CI 27.7–44.1) in the albendazole group, 82.9% (78.2–87.5) in FDC×1, and 97.2% (95.2–99.3) in FDC×3. For hookworms, cure rates were 65.1% (56.0–74.2) with albendazole, 79.8% (72.8–86.9) with FDC×1, and 95.0% (91.1–98.9) with FDC×3. Egg reduction rates in FDC arms consistently surpassed those of albendazole alone, especially for multi-day dosing. The sample size for S. stercoralis was insufficient to power a definitive efficacy conclusion, though ivermectin-containing arms trended toward favorable results. Palatability questionnaires indicated the orodispersible FDC was well accepted in taste, texture, and overall ease of administration.

Conclusions: A new co-formulation of albendazole plus ivermectin delivered at higher, fixed doses demonstrated an excellent safety profile and superior efficacy against T. trichiura and hookworms compared with albendazole monotherapy. This approach may streamline programmatic control of multiple STH species, including S. stercoralis, while contributing to reduced transmission in endemic communities.

Implications for Practice: For mass deworming initiatives, a single-dose FDC offers improved cure rates over albendazole alone while preserving simplicity. Where higher efficacy is critical—such as programs targeting near-elimination goals or in clinical settings—the three-day regimen may be preferable. Nonetheless, implementation feasibility, cost considerations, and further confirmation of efficacy against S. stercoralis and other co-endemic parasites remain important next steps.

Study Strengths and Limitations: Strengths include a multicenter design across three countries and a rigorous adaptive protocol that assessed both safety and efficacy. Limitations include the lack of blinding for participants and care providers (though outcome assessors were blinded), the underpowered sample size for S. stercoralis, and reliance on single-stool diagnostics, which may underestimate residual infections.

Future Research: Additional large-scale studies should confirm these findings in varied geographic regions and evaluate the cost-effectiveness of both single-dose and multi-day FDC strategies. Integrating albendazole–ivermectin with treatment programs for other neglected tropical diseases (e.g., onchocerciasis) could further amplify public health benefits. Genomic and pharmacokinetic analyses will clarify resistance patterns and optimize dosing regimens for broader implementation.

Reference: Krolewiecki A, Kepha S, Fleitas PE, van Lieshout L, Gelaye W, Messa A Jr, et al. “Albendazole–ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.” The Lancet Infectious Diseases. Published January 10, 2025. DOI: https://doi.org/10.1016/S1473-3099(24)00669-8

 

Network Meta-analysis: Oseltamivir Fails to Improve Key Outcomes in Nonsevere Influenza

20 Jan, 2025 | 11:17h | UTC

Background: Influenza causes significant respiratory morbidity and can lead to severe complications, especially in high-risk individuals. Current guidelines endorse antiviral therapy, yet the evidence for reducing mortality, hospital admission, and symptom duration in nonsevere cases remains controversial. Recent recommendations have often focused on neuraminidase inhibitors (e.g., oseltamivir), despite uncertainties regarding clinical impact and adverse effects. An editorial accompanying this study underscores the need to reexamine routine antiviral use, especially oseltamivir, given minimal benefit observed in outpatient populations.

Objective: To assess and compare the efficacy and safety of direct-acting antiviral medications (baloxavir, oseltamivir, laninamivir, zanamivir, peramivir, umifenovir, favipiravir, and amantadine) in treating patients with nonsevere influenza.

Methods: This systematic review and network meta-analysis included 73 randomized clinical trials (N=34,332) that evaluated antivirals vs placebo, standard care, or another antiviral. Eligible studies enrolled nonhospitalized patients with confirmed or suspected influenza. Outcomes included mortality, hospital admission, time to symptom alleviation, adverse events, and emergence of antiviral resistance. Risk of bias was assessed with a modified Cochrane tool, and the certainty of evidence was rated using the GRADE approach. Pooled estimates were generated with a frequentist random-effects model, focusing on both absolute risk differences and relative measures.

Results:

  • Mortality: Across all antiviral agents, there was high-certainty evidence of little or no effect on mortality in both low-risk and high-risk patients compared with standard care or placebo.
  • Hospital Admission: In low-risk patients, none of the antivirals significantly altered admission rates (high certainty). In high-risk patients, oseltamivir had little or no effect on hospitalization (high certainty), whereas baloxavir may reduce admissions (low certainty).
  • Time to Alleviation of Symptoms: Baloxavir shortened symptom duration by approximately one day (moderate certainty) without increasing adverse events. Oseltamivir and zanamivir likely produced smaller decreases (<1 day; moderate certainty). Umifenovir may also shorten symptoms (low certainty).
  • Adverse Events: Baloxavir did not increase treatment-related adverse events (high certainty) but may lead to viral resistance in around 10% of cases (low certainty). Oseltamivir probably increases adverse events such as nausea and vomiting (moderate certainty).
  • Serious Outcomes (ICU Admission, Duration of Hospitalization): Data were limited, with uncertainty regarding meaningful reductions in these measures.

Conclusions: Baloxavir may reduce hospital admissions for high-risk patients and significantly shorten symptom duration without notable treatment-related adverse events. Oseltamivir shows little effect on mortality or hospitalization for nonsevere influenza, with only modest (likely not clinically important) reductions in symptom duration and a higher rate of adverse events. Other antivirals either demonstrate uncertain clinical benefits or likely provide no major advantages in this patient population.

Implications for Practice: These findings suggest that routine use of oseltamivir for outpatients with nonsevere influenza should be reconsidered, especially in low-risk groups. Baloxavir appears favorable for high-risk patients, though clinicians should monitor potential drug resistance. Given the minimal impact on major outcomes and the cost considerations, prescribers should weigh the benefits and harms of these antivirals, aligning treatment decisions with patient risk profiles and clinical judgment.

Study Strengths and Limitations: Strengths include a comprehensive search, large pooled population, and rigorous GRADE-based analysis of certainty. Limitations involve low event rates for hospital admissions and mortality, limiting power for certain outcomes, and sparse data on some antivirals (e.g., amantadine). Additionally, few trials reported ICU admissions or mechanical ventilation needs, restricting conclusions about severe complications.

Future Research: Further high-quality studies should evaluate patient-important outcomes such as mechanical ventilation and severe complications in diverse populations. Investigations into combination strategies, alternative dosing, and resistance patterns would help clarify the long-term viability of baloxavir and other antivirals, particularly in high-risk cohorts.

Reference:

  1. Gao Y, Zhao Y, Liu M, et al. Antiviral Medications for Treatment of Nonsevere Influenza: A Systematic Review and Network Meta-Analysis. JAMA Internal Medicine. Published online January 13, 2025. DOI: http://doi.org/10.1001/jamainternmed.2024.7193
  2. Baghdadi JD, Grady D, Morgan DJ. The Limited Role for Antiviral Therapy in Influenza. JAMA Internal Medicine. Published online January 13, 2025. DOI: http://doi.org/10.1001/jamainternmed.2024.7258

 

2024 Focused Guideline Update on Corticosteroid Use in Sepsis, ARDS, and Community-Acquired Pneumonia

13 Jan, 2025 | 11:04h | UTC

Introduction: This summary presents the key points from a 2024 focused update of the guidelines on corticosteroid use for hospitalized adult patients with sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). Developed by a panel of international experts in critical care, endocrinology, and methodology, the update aims to incorporate new evidence into recommendations regarding dosage, duration, and timing of corticosteroid therapy. Pediatric-specific recommendations could not be made due to limited data.

Key Recommendations:

  1. Sepsis and Septic Shock
    • Conditional Recommendation: In adult patients with septic shock requiring vasopressor support, the panel suggests administering corticosteroids (typically hydrocortisone 200–300 mg/day IV for about 5–7 days, with or without fludrocortisone).
    • Strong Recommendation Against High Dose/Short Duration: High-dose corticosteroids (> 400 mg/day hydrocortisone equivalent given for fewer than 3 days) are not recommended, as they confer increased risk of adverse effects without demonstrating benefit.
  2. Acute Respiratory Distress Syndrome (ARDS)
    • Conditional Recommendation: In adult patients hospitalized with ARDS (including those with COVID-19 ARDS), the panel suggests using corticosteroids (e.g., methylprednisolone, dexamethasone, or hydrocortisone) to lower short-term mortality and potentially reduce duration of mechanical ventilation. No specific agent or dosing regimen is mandated; choices should be guided by clinical judgment and patient context.
  3. Community-Acquired Pneumonia (CAP)
    • Strong Recommendation (Severe CAP): In adults hospitalized with severe bacterial CAP, the panel recommends corticosteroids (commonly moderate-dose IV hydrocortisone or methylprednisolone for 5–7 days). Recent data indicate a clear mortality benefit in these high-risk patients.
    • No Recommendation (Less Severe CAP): For adults with less severe bacterial CAP, current evidence is inconclusive regarding mortality benefit. Although some findings suggest improvements in certain outcomes, the panel reached no consensus on whether corticosteroids should be routinely administered.

Conclusion: These updated guidelines emphasize the overall safety and potential survival benefits of corticosteroids in specific populations with critical illness, particularly those with septic shock, ARDS, or severe CAP. For each condition, the recommendations balance desirable effects—such as reduced mortality, organ dysfunction, and length of hospital stay—against possible harms, including hyperglycemia and neuromuscular weakness. Evidence remains insufficient to support pediatric guidance or clarify whether less severe CAP consistently merits treatment. Future research should address optimal dosing strategies, pediatric outcomes, long-term adverse effects, and potential cost-effectiveness across diverse healthcare settings.

Reference:
Chaudhuri, Dipayan MD, MSc, FRCPC, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Critical Care Medicine 52(5): e219–e233, May 2024. DOI: http://dx.doi.org/10.1097/CCM.0000000000006172

 

ATS Guidelines on Invasive Pulmonary Aspergillosis and Antifungal Strategies in Critically Ill Adults

7 Jan, 2025 | 12:29h | UTC

Introduction: This summary provides an overview of a recent American Thoracic Society clinical practice guideline addressing two core questions in adult pulmonary and critical care practice. First, it examines whether combination therapy with a mold-active triazole (most data concern voriconazole, though newer agents such as isavuconazole or posaconazole may also be considered) plus an echinocandin (specifically caspofungin, micafungin, or anidulafungin) offers added benefit over mold-active triazole monotherapy for patients with proven or probable invasive pulmonary aspergillosis (IPA). Second, it evaluates whether routine use of prophylactic or empiric antifungal agents against Candida species is advisable in critically ill, nonneutropenic, nontransplant patients at risk of invasive candidiasis (IC). By synthesizing available evidence using the GRADE approach, this guideline aims to support clinicians in optimizing therapeutic strategies and improving patient outcomes in these complex infections.

Key Recommendations:

Initial Combination Therapy vs. Monotherapy for IPA

  • For patients with proven or probable IPA, the guideline makes a conditional recommendation, meaning the best choice isn’t entirely clear. Both initial combination therapy (mold-active triazole + echinocandin) and monotherapy (mold-active triazole alone) are considered reasonable options.
  • Evidence stems primarily from studies in hematologic malignancy (HM) or hematopoietic stem cell transplant (HSCT) recipients, with mixed findings in observational cohorts and a key randomized trial favoring combination therapy, particularly in a subgroup diagnosed by positive galactomannan assays.
  • When critical illness or triazole resistance is a concern, combination therapy may be considered, but there is insufficient evidence to categorically endorse one approach over the other.

Prophylactic or Empiric Antifungal Therapy for Candida in Critically Ill Patients

  • In nonneutropenic, nontransplant adult ICU patients at risk for IC, the guideline makes a conditional recommendation against routinely using prophylactic or empiric antifungal therapy. This means the benefits of withholding these treatments likely outweigh the risks, but there’s still some uncertainty.
  • Low-quality evidence from multiple randomized controlled trials showed no significant mortality benefit in administering antifungals prophylactically or empirically compared with placebo.
  • Although IC carries substantial morbidity and mortality, its overall incidence in this population remains low, and ongoing surveillance or targeted diagnostics may be preferable to universal antifungal administration.

Conclusion: The panel emphasizes that these recommendations should be applied with clinical judgment, especially in patients with severe disease, likely high fungal burden, or concerns for antifungal resistance. Combination therapy for IPA may be particularly relevant when critical illness or limited triazole efficacy is suspected. Meanwhile, prophylactic or empiric anti-Candida therapy in the broader ICU setting does not appear to substantially reduce mortality. Continued advances in rapid diagnostics, close monitoring of local resistance patterns, and new antifungal agents may further refine best practices. Future research should focus on validating these findings in diverse patient populations, exploring novel combination regimens, and establishing more precise risk assessments for IC in the ICU.

Reference: Epelbaum O, Marinelli T, Haydour Q, Pennington KM, Evans SE, Carmona EM, Husain S, Knox KS, Jarrett BJ, Azoulay E, Hope WW, and others. “Treatment of Invasive Pulmonary Aspergillosis and Preventive and Empirical Therapy for Invasive Candidiasis in Adult Pulmonary and Critical Care Patients: An Official American Thoracic Society Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine (2025). https://doi.org/10.1164/rccm.202410-2045ST

RCT: Assessing Procalcitonin-Based Antibiotic Management in Critically Ill Patients With Sepsis

7 Jan, 2025 | 14:00h | UTC

Background: Optimal antibiotic duration for sepsis remains uncertain. Procalcitonin (PCT) and C-reactive protein (CRP) are thought to support shorter courses, but prior research was small-scale or at risk of bias. This multicenter, randomized trial (ADAPT-Sepsis) evaluated whether daily PCT- or CRP-guided protocols could reduce antibiotic use without increasing 28-day all-cause mortality in critically ill adults with suspected sepsis.

Objective: To determine if daily biomarker-guided (PCT or CRP) strategies decrease total antibiotic days among critically ill adults while maintaining acceptable 28-day mortality, compared with standard care.

Methods: From 2018 to 2024 (with enrollment paused March–August 2020 due to COVID-19), 2760 adults (≥18 years) on intravenous antibiotics for suspected sepsis (acute organ dysfunction and presumed infection) and likely to continue antibiotics for at least 72 hours were randomized across 41 UK NHS ICUs within 24 hours of antibiotic initiation. They were assigned in a 1:1:1 ratio to (1) daily PCT-guided advice (n=918), (2) daily CRP-guided advice (n=924), or (3) standard care (n=918). Biomarker results were concealed; clinicians received automated daily prompts recommending continuation or discontinuation. The co-primary outcomes were (1) total antibiotic duration (randomization to day 28) and (2) 28-day all-cause mortality. Secondary measures included antibiotic duration for the initial sepsis episode, 90-day mortality, readmissions, and length of stay.

Results: Among 2760 participants (mean age, 60.2 years; 60.3% men; ~50% with septic shock), over 96% provided 28-day data. Patients in the PCT-guided arm had a statistically significant mean reduction in total antibiotic duration vs standard care (9.8 vs 10.7 days; difference, 0.88 days; 95% CI, 0.19–1.58; p=0.01). The PCT strategy met the prespecified 5.4% noninferiority margin for 28-day mortality (20.9% vs 19.4%; absolute difference, 1.57; 95% CI, –2.18 to 5.32; p=0.02), implying noninferiority but not fully excluding a small risk of excess mortality. CRP-guided protocols did not shorten total antibiotic use (10.6 vs 10.7 days; p=0.79) and were inconclusive for noninferiority regarding mortality (21.1% vs 19.4%; difference, 1.69; 95% CI, –2.07 to 5.45; p=0.03). Notably, 90-day mortality also showed no significant differences. A post-trial commentary (PulmCCM) emphasized that some uncertainty remains with the 5.4% margin and warned that patient-level randomization could subtly discourage earlier antibiotic discontinuation in standard care, which received no explicit “stop” prompts.

Conclusions: In critically ill patients with suspected sepsis, a PCT-guided antibiotic discontinuation protocol shortened overall antibiotic use by nearly one day without exceeding the predefined noninferiority threshold for 28-day mortality. However, the chosen 5.4% margin allows for the possibility of clinically relevant harm. A CRP-guided protocol did not reduce total antibiotic use and showed inconclusive mortality findings.

Implications for Practice: Adopting PCT-based stewardship may modestly decrease antibiotic exposure without a clear short-term mortality penalty, potentially limiting antibiotic resistance. Clinicians should remain vigilant, recognizing the risk tolerance implied by the 5.4% margin. PCT results should complement, not replace, comprehensive clinical judgment.

Study Strengths and Limitations: Strengths include the large sample size, multi-center design, blinded biomarker allocation, and distinct emphasis on both effectiveness and safety outcomes. Limitations include the acceptance of a 5.4% potential excess mortality as the noninferiority threshold, uncertainty about rare but significant harms, and the possibility of bias introduced by patient-level randomization. Generalizability to lower-resource settings may also be limited.

Future Research: Further randomized trials with lower noninferiority margins or cluster-level allocation are needed to better define the safety and efficacy of PCT-guided strategies for reducing antibiotic duration in sepsis. Additional investigations are needed for long-term patient-centered outcomes, cost-effectiveness, and the role of alternative biomarkers or combined strategies in sepsis care.

Reference:

Dark P, Hossain A, McAuley DF, et al. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial. JAMA. 2024; published online December 9. DOI: http://doi.org/10.1001/jama.2024.26458

PulmCCM Commentary: “Is procalcitonin ‘safe’ to guide antibiotic use in patients with sepsis? ADAPT-Sepsis tests the strategy in the U.K., with global ambitions.” Jan 02, 2025. https://www.pulmccm.org/p/is-procalcitonin-safe-to-guide-antibiotic

Management of Adult Sepsis in Resource-Limited Settings: A Global Delphi-Based Consensus

26 Dec, 2024 | 02:06h | UTC

Introduction: This summary presents key points from a recent expert consensus on managing adult sepsis under limited-resource conditions, where patients may lack access to an ICU bed, advanced monitoring technologies, or sufficient staffing. The statements were developed through a Delphi process involving an international panel of clinicians, aiming to complement existing sepsis guidelines by focusing on pragmatic approaches and context-specific adaptations. These consensus statements address unique challenges such as limited diagnostic tests, alternative strategies for hemodynamic monitoring, and management of sepsis in areas with tropical infections.

Key Recommendations:

  1. Location of Care and Transfer
    • When an ICU bed is unavailable, care can be provided in a non-ICU setting if minimum monitoring (neurological status, blood pressure, peripheral perfusion) is ensured.
    • Before transferring a patient, ensure airway patency, initiate intravenous fluids and antimicrobials, and maintain safe transport conditions.
    • Incorporate telemedicine or phone consultation with critical care specialists whenever feasible.
  2. Diagnostic Considerations
    • Employ screening tools (e.g., qSOFA) in areas with limited resources, acknowledging its diagnostic constraints.
    • Use clinical parameters like altered mental state, capillary refill time (CRT), and urine output to gauge tissue perfusion when lactate measurement is unavailable.
    • Insert an indwelling urinary catheter in septic shock to monitor urine output accurately, balancing infection risks against close monitoring needs.
  3. Hemodynamic Management
    • Rely on clinical indicators (CRT, urine output) to guide fluid resuscitation when serum lactate is not accessible.
    • Use fluid responsiveness tests (e.g., passive leg raising, pulse pressure variation) if advanced hemodynamic monitoring is impractical.
    • Consider balanced solutions such as Ringer’s lactate or Hartmann’s solution for fluid resuscitation.
    • Recognize that patients with tropical infections (e.g., malaria, dengue) may require cautious fluid volumes to avoid overload.
    • Initiate epinephrine if norepinephrine or vasopressin is unavailable, and use vasopressors through peripheral lines if central access cannot be established.
  4. Antimicrobial Therapy
    • Administer antibiotics without delay (ideally within one hour) in suspected sepsis or septic shock.
    • In severe infections of parasitic origin (e.g., malaria), start antiparasitic agents promptly.
    • In settings where laboratory investigations are limited, begin broad-spectrum antimicrobial coverage when infection cannot be ruled out.
    • De-escalate or discontinue therapy based on clinical improvement, declining white blood cell counts, and adequate source control.
  5. Respiratory Support
    • For acute hypoxemic respiratory failure in septic patients, noninvasive ventilation (NIV) can be used if high-flow nasal oxygen is not available, provided close monitoring for potential failure is ensured.

Conclusion: These consensus-based statements offer practical guidance for clinicians treating sepsis in resource-limited environments. By adapting globally accepted recommendations and incorporating alternative strategies—such as clinical markers of perfusion, use of peripheral vasopressors, and prioritizing immediate antimicrobial therapy—these principles aim to improve patient outcomes where healthcare resources are scarce. Further research and context-specific adaptations will be essential to address remaining uncertainties and refine these expert recommendations.

Reference:
Thwaites, L., Nasa, P., Abbenbroek, B. et al. Management of adult sepsis in resource-limited settings: global expert consensus statements using a Delphi method. Intensive Care Medicine (2024). https://doi.org/10.1007/s00134-024-07735-7

 

Guideline: Doxycycline Postexposure Prophylaxis to Reduce Bacterial STI Incidence in High-Risk Populations

19 Dec, 2024 | 22:32h | UTC

Introduction: This summary presents key recommendations from the 2024 Centers for Disease Control and Prevention (CDC) guidelines on using doxycycline postexposure prophylaxis (doxyPEP) to prevent bacterial sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. Targeting men who have sex with men (MSM) and transgender women with at least one bacterial STI in the past 12 months, these guidelines aim to reduce recurrence rates and improve sexual health outcomes through timely prophylactic intervention.

Key Recommendations:

  1. Offer doxyPEP counseling to MSM and transgender women with a recent bacterial STI history, addressing the benefits, harms, and uncertainties of prophylactic doxycycline use.
  2. Advise eligible patients to take a single 200 mg dose of doxycycline as soon as possible (ideally within 72 hours) following condomless oral, anal, or vaginal sexual exposure to reduce their subsequent STI risk.
  3. Reinforce periodic screening (every 3–6 months) for STI markers, including syphilis and HIV serologies, as well as nucleic acid amplification tests for gonorrhea and chlamydia at relevant anatomical sites.
  4. Integrate doxyPEP into comprehensive sexual health services that include risk-reduction counseling, condom use, recommended immunizations, and linkage to HIV preexposure prophylaxis (PrEP) or HIV care, thereby enhancing overall prevention strategies.
  5. Consider extending doxyPEP to other high-risk groups, including heterosexual individuals with recurrent STIs, guided by clinical judgment and shared decision-making.
  6. Monitor and address adverse events, particularly gastrointestinal symptoms, and acknowledge the potential for antimicrobial resistance. Continued vigilance is warranted given the risk of resistance in commensal flora and key STI pathogens, such as Neisseria gonorrhoeae.
  7. Assess social and ethical dimensions of doxyPEP implementation, ensuring equitable access and minimizing potential harms, including stigma or intimate partner violence related to prophylaxis disclosure.

Conclusion: Implementing doxyPEP for MSM and transgender women who have experienced a recent bacterial STI can substantially lower the incidence of recurrent infections. By combining prophylactic doxycycline with routine surveillance, comprehensive preventive services, and careful consideration of resistance patterns, clinicians may enhance patient care and strengthen STI control efforts. Further investigation is needed to establish efficacy in cisgender women, transgender men, nonbinary persons, and other populations at risk. Longer-term, population-based studies focused on antimicrobial resistance and community-level effects will help guide sustainable and equitable use of this prevention strategy.

Reference: Flores J, Davis AM, Hazra A. Doxycycline Postexposure Prophylaxis to Prevent Bacterial Sexually Transmitted Infection. JAMA. Published online December 19, 2024. DOI: http://doi.org/10.1001/jama.2024.24540

 

RCT: A Single Dose of Ceftriaxone Reduces Early Ventilator-Associated Pneumonia in Acute Brain Injury Patients

17 Dec, 2024 | 12:26h | UTC

Background: Patients with acute brain injury are at increased risk for early ventilator-associated pneumonia (VAP), which can worsen their clinical course. Although short-term antibiotic prophylaxis has been considered, its utility remains uncertain. This study evaluated whether a single early dose of ceftriaxone could reduce the incidence of early VAP in these patients.

Objective: To determine if a single 2-g intravenous dose of ceftriaxone administered within 12 hours of intubation reduces the incidence of early VAP (day 2 to day 7 of mechanical ventilation) in comatose adults (Glasgow Coma Scale ≤12) requiring prolonged mechanical ventilation after acute brain injury.

Methods: This multicenter, randomized, double-blind, placebo-controlled, assessor-masked superiority trial was conducted in nine ICUs across eight French university hospitals. Patients with acute brain injury from trauma, stroke, or subarachnoid hemorrhage who required at least 48 hours of mechanical ventilation were enrolled. Participants received either ceftriaxone 2 g or placebo once, early after endotracheal intubation. All patients received standard VAP prevention measures, but no selective oropharyngeal or digestive decontamination. The primary endpoint was the incidence of early VAP confirmed by blinded assessors using standard clinical, radiological, and microbiological criteria.

Results: Among 319 patients included in the analysis (162 ceftriaxone, 157 placebo), early VAP incidence was significantly lower with ceftriaxone (14%) compared to placebo (32%) (HR 0.60 [95% CI 0.38–0.95]; p=0.030). Patients receiving ceftriaxone had fewer overall VAP episodes, fewer ventilator and antibiotic exposure days, shorter ICU and hospital stays, and reduced 28-day mortality (15% vs 25%). No significant increase in resistant organisms or adverse events attributable to ceftriaxone was observed.

Conclusions: A single early dose of ceftriaxone significantly reduced early VAP risk in acute brain injury patients undergoing mechanical ventilation. This prophylactic approach may improve clinical outcomes without evident safety concerns.

Implications for Practice: Incorporating a single early ceftriaxone dose into VAP prevention protocols for brain-injured patients could mitigate early respiratory infections and potentially enhance clinical outcomes. Nonetheless, clinicians should remain cautious, considering overall antibiotic stewardship and the need for further evidence on long-term microbial resistance patterns.

Study Strengths and Limitations: Strengths include a robust, multicenter, double-blind, placebo-controlled design and blinded adjudication of VAP cases. Limitations include the lack of long-term assessment of the intestinal microbiota and antimicrobial resistance. Further investigation is required to confirm the safety profile regarding microbial ecology and to explore neurological outcomes in greater depth.

Future Research: Future studies should examine the long-term effects of this single-dose approach on resistance patterns, microbial flora, and functional neurological recovery.

Reference: Dahyot-Fizelier C, et al. Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial. The Lancet Respiratory Medicine. 2024; DOI: http://doi.org/10.1016/S2213-2600(23)00471-X

 

Management of Adult Sepsis in Resource-Limited Settings: A Global Delphi-Based Consensus

24 Dec, 2024 | 13:35h | UTC

Introduction: This summary presents key points from a recent expert consensus on managing adult sepsis under limited-resource conditions, where patients may lack access to an ICU bed, advanced monitoring technologies, or sufficient staffing. The statements were developed through a Delphi process involving an international panel of clinicians, aiming to complement existing sepsis guidelines by focusing on pragmatic approaches and context-specific adaptations. These consensus statements address unique challenges such as limited diagnostic tests, alternative strategies for hemodynamic monitoring, and management of sepsis in areas with tropical infections.

Key Recommendations:

  1. Location of Care and Transfer
    • When an ICU bed is unavailable, care can be provided in a non-ICU setting if minimum monitoring (neurological status, blood pressure, peripheral perfusion) is ensured.
    • Before transferring a patient, ensure airway patency, initiate intravenous fluids and antimicrobials, and maintain safe transport conditions.
    • Incorporate telemedicine or phone consultation with critical care specialists whenever feasible.
  2. Diagnostic Considerations
    • Employ screening tools (e.g., qSOFA) in areas with limited resources, acknowledging its diagnostic constraints.
    • Use clinical parameters like altered mental state, capillary refill time (CRT), and urine output to gauge tissue perfusion when lactate measurement is unavailable.
    • Insert an indwelling urinary catheter in septic shock to monitor urine output accurately, balancing infection risks against close monitoring needs.
  3. Hemodynamic Management
    • Rely on clinical indicators (CRT, urine output) to guide fluid resuscitation when serum lactate is not accessible.
    • Use fluid responsiveness tests (e.g., passive leg raising, pulse pressure variation) if advanced hemodynamic monitoring is impractical.
    • Consider balanced solutions such as Ringer’s lactate or Hartmann’s solution for fluid resuscitation.
    • Recognize that patients with tropical infections (e.g., malaria, dengue) may require cautious fluid volumes to avoid overload.
    • Initiate epinephrine if norepinephrine or vasopressin is unavailable, and use vasopressors through peripheral lines if central access cannot be established.
  4. Antimicrobial Therapy
    • Administer antibiotics without delay (ideally within one hour) in suspected sepsis or septic shock.
    • In severe infections of parasitic origin (e.g., malaria), start antiparasitic agents promptly.
    • In settings where laboratory investigations are limited, begin broad-spectrum antimicrobial coverage when infection cannot be ruled out.
    • De-escalate or discontinue therapy based on clinical improvement, declining white blood cell counts, and adequate source control.
  5. Respiratory Support
    • For acute hypoxemic respiratory failure in septic patients, noninvasive ventilation (NIV) can be used if high-flow nasal oxygen is not available, provided close monitoring for potential failure is ensured.

Conclusion: These consensus-based statements offer practical guidance for clinicians treating sepsis in resource-limited environments. By adapting globally accepted recommendations and incorporating alternative strategies—such as clinical markers of perfusion, use of peripheral vasopressors, and prioritizing immediate antimicrobial therapy—these principles aim to improve patient outcomes where healthcare resources are scarce. Further research and context-specific adaptations will be essential to address remaining uncertainties and refine these expert recommendations.

Reference:
Thwaites, L., Nasa, P., Abbenbroek, B. et al. Management of adult sepsis in resource-limited settings: global expert consensus statements using a Delphi method. Intensive Care Medicine (2024). https://doi.org/10.1007/s00134-024-07735-7

 

Review: Candida auris Infections

24 Nov, 2024 | 19:50h | UTC

Introduction: 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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.

Reference: Lionakis MS, Chowdhary A. Candida auris Infections. New England Journal of Medicine. 2024; DOI: http://doi.org/10.1056/NEJMra2402635

 

RCT: 7-Day Antibiotic Therapy Noninferior to 14-Day for Bloodstream Infections

20 Nov, 2024 | 18:19h | UTC

Background: 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.

Reference: The BALANCE Investigators, for the Canadian Critical Care Trials Group and others. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. New England Journal of Medicine. Published November 20, 2024. DOI: http://doi.org/10.1056/NEJMoa2404991

 

Retrospective Cohort Study: Midline Catheters Associated with Lower Major Complications Than PICCs in Outpatient Antimicrobial Therapy

16 Nov, 2024 | 14:35h | UTC

Background: 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.

Reference: Paje D, et al. Midline vs Peripherally Inserted Central Catheter for Outpatient Parenteral Antimicrobial Therapy. JAMA Internal Medicine. 2024. DOI: http://doi.org/10.1001/jamainternmed.2024.5984

 

News Release: Seven-Day Antibiotic Regimen Effective for Bloodstream Infections

10 Nov, 2024 | 17:54h | UTC

Introduction: 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 | UTC

Introduction: 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:

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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.

Reference: Nelson Z, Aslan AT, Beahm NP, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Network Open. 2024;7(11). DOI: http://doi.org/10.1001/jamanetworkopen.2024.44495

 

Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines

12 Oct, 2024 | 18:23h | UTC

Introduction: 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:

  1. 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)
  2. 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)
  3. 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)
  4. 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)
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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.

Reference: Aithal GP, Palaniyappan N, China L, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70(1):9–29. DOI: http://doi.org/10.1136/gutjnl-2020-321790

 

Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD

6 Oct, 2024 | 17:12h | UTC

Background: 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.

Reference: Kuijpers SME, et al. (2024) The evidence base for the optimal antibiotic treatment duration of upper and lower respiratory tract infections: an umbrella review. Lancet Infect Dis. DOI: http://doi.org/10.1016/S1473-3099(24)00456-0

RCT: H. pylori Screening Added to Fecal Immunochemical Testing Did Not Reduce Gastric Cancer Incidence or Mortality

4 Oct, 2024 | 11:00h | UTC

Background: 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.

Reference: Lee Y-C, et al. (2024) Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.14887

 

Summary: Community-Acquired Pneumonia

19 Sep, 2024 | 17:21h | UTC

Introduction

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.
  • 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

  1. 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.
  2. 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.
  3. 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.
  4. Antimicrobial Stewardship:
    • Reassess antibiotic therapy daily and de-escalate based on clinical response and microbiological data.
    • Transition to oral antibiotics when appropriate.
  5. 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.

Reference: Vaughn VM, Dickson RP, Horowitz JK, Flanders SA. Community-Acquired Pneumonia: A Review. JAMA. Published online September 16, 2024. doi:10.1001/jama.2024.14796

 

Innovative Antimicrobial Susceptibility Testing Bypasses Blood Culture, Promising Faster Sepsis Diagnosis – Nature

18 Aug, 2024 | 14:09h | UTC

Study 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.

Reference: Kim, T. H., Kang, J., Jang, H., Joo, H., Lee, G. Y., Kim, H., et al. (2024). Blood culture-free ultra-rapid antimicrobial susceptibility testing. Nature, (2024).

 

Review: Prevention and Management of Device-Associated Complications in the Intensive Care Unit – The BMJ

17 Aug, 2024 | 20:04h | UTC

Introduction:

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.

Reference: Hixson, R., Jensen, K. S., Melamed, K. H., & Qadir, N. (2024). Device associated complications in the intensive care unit. BMJ, 386, e077318. http://dx.doi.org/10.1136/bmj-2023-077318

 

Meta-Analysis: Inhaled Antibiotics Offer Modest Reductions in Exacerbations and Quality of Life Gains in Bronchiectasis – CHEST

11 Aug, 2024 | 13:12h | UTC

Study 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.

Reference: Cordeiro, R., Choi, H., Haworth, C. S., & Chalmers, J. D. (2024). The Efficacy and Safety of Inhaled Antibiotics for the Treatment of Bronchiectasis in Adults. CHEST Journal, 166(1), 61-80. DOI: https://doi.org/10.1016/j.chest.2024.01.045.

 

Nested Case-Control Study: Sulfonamide Antibiotics and Cephalosporins Linked to Highest Risk of Serious Cutaneous Adverse Drug Reactions – JAMA

10 Aug, 2024 | 21:16h | UTC

Study 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.

Reference: Lee EY et al. (2024). Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions. JAMA. Published online August 8, 2024. DOI: 10.1001/jama.2024.11437.

 

IDSA 2024 Guidelines for Treatment of Antimicrobial-Resistant Gram-Negative Infections – Clin Infect Dis

10 Aug, 2024 | 20:16h | UTC

Introduction:

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:

Tamma, P. D., Heil, E. L., Justo, J. A., Mathers, A. J., Satlin, M. J., & Bonomo, R. A. (2024). Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clinical Infectious Diseases.

 

Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open

25 May, 2024 | 19:55h | UTC

This randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.

 

Reference (link to free full-text):

Grzegorz Raba et al. (2024). Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis A Randomized Clinical Trial. JAMA Netw Open, 7(5), e248661. DOI: 10.1001/jamanetworkopen.2024.8661

 

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