Antibiotic Stewardship
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.
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.
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.
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:
Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open
25 May, 2024 | 19:55h | UTCThis 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):
RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J
6 May, 2024 | 06:32h | UTCThis randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.
Reference (link to abstract – $ for full-text):
RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med
6 May, 2024 | 06:28h | UTCThis randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.
Reference (link to free full-text):
SCCM/IDSA Updated guidelines for evaluating new fever in adult ICU patients – Crit Care Med
5 May, 2024 | 15:12h | UTCThe 2023 revision of the guidelines for assessing new-onset fever in adult ICU patients stresses rigorous diagnostic processes using the GRADE methodology. These guidelines, developed without industry funding, offer 12 recommendations and nine best-practice statements focused primarily on the accurate measurement of core body temperature and initial diagnostic evaluations geared towards identifying potential infectious causes. Central temperature monitoring is recommended when possible; otherwise, oral or rectal measurements are preferred. The utility of imaging studies and rapid diagnostic tests is highlighted, along with the selective use of biomarkers to guide the cessation of antimicrobial therapy. The guidelines underscore that most recommendations are based on weak evidence, thus highlighting the need for continued research in diagnostic methodologies and fever management in the ICU setting.
Reference (link to free full-text):
Systematic Review: Comparing antibiotic treatment vs. appendectomy for the initial treatment of uncomplicated appendicitis – Cochrane Library
4 May, 2024 | 13:09h | UTCStudy Design and Population:
This Cochrane review analyzed 13 randomized controlled trials involving 3,358 participants to compare the efficacy of antibiotic treatment versus appendectomy in managing uncomplicated acute appendicitis. The included studies predominantly involved adult participants and utilized broad-spectrum antibiotics, with interventions ranging from open to predominantly laparoscopic appendectomy. Data collection spanned from hospital admission to up to seven years, with studies conducted across various global regions, including Asia, Europe, and North America.
Main Findings:
The primary outcomes revealed that antibiotic treatment might slightly increase the risk of unsuccessful treatment with 76 additional unsuccessful cases per 1,000 individuals compared to surgery, though these results did not reach clinical significance. Antibiotics reduced wound infections but possibly increased the average hospital stay by half a day. About 30.7% of participants treated with antibiotics required an appendectomy within one year. Secondary outcomes showed very uncertain evidence on antibiotics’ effect on intra-abdominal abscess or reoperation rates, and a slight increase in negative appendectomy rates was observed.
Implications for Practice:
The findings suggest that while antibiotics could serve as an initial treatment to avoid surgery in two-thirds of cases annually, a significant portion may still require surgical intervention. This information is crucial for clinicians in making informed treatment decisions, particularly considering patient preferences and the risk of surgery. Further research is needed to explore long-term outcomes and identify patient subgroups that may benefit most from either treatment.
Reference (link to abstract – $ for full-text):
M-A: Reduced risk of infective endocarditis following dental procedures with antibiotic prophylaxis in high-risk individuals
26 Apr, 2024 | 12:07h | UTCStudy Design and Population:
This systematic review and meta-analysis evaluated the impact of antibiotic prophylaxis on the incidence of infective endocarditis following invasive dental procedures. Researchers analyzed data from 1,152,345 cases sourced from PubMed, Cochrane-CENTRAL, Scopus, and other databases up to May 2023. The study included various research designs, such as case-control, cohort, and time-trend studies, assessing the effectiveness of antibiotic prophylaxis across different risk groups.
Main Findings:
The meta-analysis revealed that antibiotic prophylaxis significantly lowers the risk of infective endocarditis among individuals at high risk (pooled relative risk, 0.41; 95% CI, 0.29-0.57), with consistent findings across studies of good quality. However, the effectiveness of prophylaxis in individuals at moderate or low/unknown risk remains unsupported by sufficient evidence. Time-trend studies provided mixed results, with some indicating no change or an increase in infective endocarditis incidence post-guideline changes in 2007.
Implications for Practice:
The findings support the continued use of antibiotic prophylaxis for high-risk individuals undergoing invasive dental procedures, aligning with current guidelines from the American Heart Association and European Society of Cardiology. The lack of clear benefits in moderate and low-risk groups suggests a need for further research to optimize prophylaxis guidelines and ensure effective risk stratification in clinical practice.
Reference (link to abstract – $ for full-text):
FDA approves antibiotic Zevtera (ceftobiprole medocaril sodium) for three indications
26 Apr, 2024 | 11:39h | UTCThe FDA has granted approval for Zevtera (ceftobiprole medocaril sodium), an antibiotic formulated for injection, targeting three key bacterial infections. This includes treatment for adults with Staphylococcus aureus bloodstream infections (SAB) with or without right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSI), and community-acquired bacterial pneumonia (CABP) in both adults and pediatric patients aged three months to under 18 years.
The approval follows rigorous clinical trials demonstrating Zevtera’s efficacy. In a multicenter study for SAB, Zevtera achieved a 69.8% success rate, slightly outperforming the comparator drug. For ABSSSI, Zevtera showed a 91.3% early clinical response, and for CABP, it had a clinical cure rate of 76.4% in adults. Pediatric efficacy for CABP was extrapolated from adult data and supported by a smaller pediatric trial.
Common side effects include anemia, nausea, and increased liver enzyme levels, with specific reactions varying by infection treated. Contraindications include severe hypersensitivity to ceftobiprole or other cephalosporins. Zevtera also carries warnings about potential hypersensitivity reactions, central nervous system effects, and Clostridioides difficile-associated diarrhea.
This approval, supported by Priority Review and Fast Track designations, offers a new treatment option for clinicians managing these serious infections.
Source: FDA NEWS RELEASE: FDA Approves New Antibiotic for Three Different Uses
Cohort Study: Inappropriate pneumonia diagnoses and associated risks in 17,290 hospitalized adults
26 Apr, 2024 | 11:25h | UTCStudy Design and Population:
This prospective cohort study analyzed medical records and patient interactions from July 2017 to March 2020 across 48 Michigan hospitals. A total of 17,290 adults admitted for general care were retrospectively assessed for community-acquired pneumonia (CAP) treatment, focusing on those who received antibiotics within the first two days of hospitalization.
Main Findings:
The study identified that 12.0% of the patients were inappropriately diagnosed with CAP. Key risk factors for misdiagnosis included older age, presence of dementia, and altered mental status at presentation. Among those misdiagnosed, 87.6% underwent a full course of antibiotics, which did not significantly change the 30-day risk of mortality, readmission, emergency visits, or Clostridioides difficile infections compared to brief treatment but was associated with higher antibiotic-related adverse events.
Implications for Practice:
The findings underscore the prevalence of inappropriate pneumonia diagnosis among hospitalized adults, especially in older patients with specific geriatric conditions. This study highlights the potential harms of unnecessary antibiotic use, suggesting a need for improved diagnostic accuracy and treatment decision-making in hospital settings to mitigate adverse outcomes.
Reference (free full-text):
RCT: Clarithromycin improves early clinical and inflammatory responses in hospitalized community-acquired pneumonia patients
23 Mar, 2024 | 20:25h | UTCStudy Design and Population: The ACCESS trial was a phase 3, prospective, double-blind, randomized controlled trial conducted in 18 Greek hospitals, involving adults hospitalized with community-acquired pneumonia who displayed systemic inflammatory response syndrome, had a Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin levels of 0.25 ng/mL or more. Participants were randomly assigned to receive either standard of care with intravenous cephalosporins or β-lactam/β-lactamase inhibitor combinations plus oral clarithromycin (500 mg twice daily for 7 days) or placebo. The trial aimed to evaluate the impact of clarithromycin on early clinical and inflammatory responses.
Main Findings: Among 278 participants allocated to clarithromycin (n=139) or placebo (n=139), the primary composite endpoint—indicating early clinical response and inflammatory burden reduction within 72 hours—was met by 68% of patients in the clarithromycin group compared to 38% in the placebo group, showcasing a significant difference (29.6%, odds ratio 3.40, p<0.0001). Serious treatment-emergent adverse events were slightly lower in the clarithromycin group than in the placebo group, although not statistically significant.
Implications for Practice: The addition of clarithromycin to the standard of care for hospitalized patients with community-acquired pneumonia significantly improves early clinical response and reduces inflammatory burden, potentially through modulation of the immune response. These results support the use of clarithromycin alongside β-lactam antibiotics in the treatment of community-acquired pneumonia, highlighting its role in enhancing patient outcomes by targeting early clinical and inflammatory indicators.
Reference
Prof Evangelos J Giamarellos-Bourboulis, MD et al. (2024). Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine, Volume(Issue), Pages. DOI: https://doi.org/10.1016/S2213-2600(23)00412-5. Access the study here: Link
Review | Artificial intelligence, machine learning and deep learning: Potential resources for the infection clinician
9 Aug, 2023 | 15:18h | UTC
Perspective | Cardiac device infection: removing barriers to timely and adequate treatment
4 Aug, 2023 | 11:54h | UTC
Position Paper | Perioperative antibiotic prophylaxis in skin surgery
3 Aug, 2023 | 13:39h | UTCPerioperative antibiotic prophylaxis in skin surgery – Position paper of the Antibiotic Stewardship working group of the German Society for Dermatologic Surgery (DGDC) – Journal of the German Society of Dermatology
Part 1: Procedure- and patient-related risk factors
Part 2: Special indications and situations
RCT | Early oral antibiotic switch in low-risk neutropenic sepsis shows mixed results
3 Aug, 2023 | 13:15h | UTC
Consensus Paper | Diagnosis and management of infective endocarditis in adults
1 Aug, 2023 | 14:34h | UTC
RCT | Limited antibiotic efficacy in children with sinusitis lacking nasopharyngeal pathogens
27 Jul, 2023 | 13:08h | UTCIdentifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial – JAMA (free for a limited period)
Editorial: Acute Bacterial Sinusitis: Limitations of Test-Based Treatment – JAMA (free for a limited period)
News Release: Bacterial testing in kids with sinusitis could slash antibiotic use – University of Pittsburgh
Commentary: Trial suggests bacterial test could reduce antibiotics in kids with sinusitis – CIDRAP
Commentary on Twitter
In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens. The antibiotic effect did not depend on the color of nasal discharge. https://t.co/hgRx1Qou53 pic.twitter.com/zYs8Mfbjjp
— JAMA (@JAMA_current) July 26, 2023
Cohort Study | 9.9% of patients acquire C. difficile carriage in healthcare facilities, most do not develop clinical infection
27 Jul, 2023 | 13:01h | UTC
Consensus Paper | Urinary tract infections in pregnant individuals
25 Jul, 2023 | 13:53h | UTCUrinary Tract Infections in Pregnant Individuals – Obstetrics & Gynecology
RCT | Long-term Doxycycline for COPD does not reduce exacerbations, except possibly in severe cases or with low eosinophils
24 Jul, 2023 | 12:50h | UTCA Double-Blind, Randomised, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable COPD – American Journal of Respiratory and Critical Care Medicine (link to abstract – $ for full-text)
RCT | Molecular screening for bacterial vaginosis does not significantly reduce preterm birth rates
21 Jul, 2023 | 13:31h | UTCSee also: Visual Abstract
IDSA 2023 Guidance on the treatment of antimicrobial resistant gram-negative infections
20 Jul, 2023 | 11:15h | UTC