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Science (New York, N.Y.) Feb 2024We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes...
We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of , , and . We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory-calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail.
Topics: Anti-Bacterial Agents; Erythromycin; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa; Bridged-Ring Compounds; Oxepins; Lincosamides; Animals; Mice; Drug Design; Ribosomes
PubMed: 38359125
DOI: 10.1126/science.adk8013 -
The Lancet. Respiratory Medicine Apr 2024Addition of macrolide antibiotics to β-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Addition of macrolide antibiotics to β-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a β-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome.
METHODS
The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of β-lactam plus β-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044).
FINDINGS
Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment.
INTERPRETATION
Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to β-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden.
FUNDING
Hellenic Institute for the Study of Sepsis and Abbott Products Operations.
Topics: Adult; Humans; Clarithromycin; Greece; Prospective Studies; Procalcitonin; Pneumonia; Anti-Bacterial Agents; Anti-Inflammatory Agents; Double-Blind Method; Treatment Outcome
PubMed: 38184008
DOI: 10.1016/S2213-2600(23)00412-5 -
International Journal of Molecular... Jul 2023Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of... (Review)
Review
The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.
Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.
Topics: Adult; Humans; Aged; Pneumonia, Pneumococcal; Prevalence; Pneumococcal Infections; Streptococcus pneumoniae; Anti-Bacterial Agents; Macrolides; Community-Acquired Infections; Cardiovascular Diseases
PubMed: 37446214
DOI: 10.3390/ijms241311038 -
Indian Journal of Medical Microbiology 2023Mycoplasmas are the smallest prokaryotic microorganisms found in nature. Mycoplasma pneumoniae (M. pneumoniae) is the most commonly studied among human mycoplasmas. (Review)
Review
BACKGROUND
Mycoplasmas are the smallest prokaryotic microorganisms found in nature. Mycoplasma pneumoniae (M. pneumoniae) is the most commonly studied among human mycoplasmas.
OBJECTIVES
In this review, we briefly focus on the recent developments that have enhanced our understanding of M. pneumoniae, one of the smallest pathogenic bacteria of great clinical importance in children.
CONTENT
M. pneumoniae infections may involve either upper or lower respiratory tract or both of them. Extrapulmonary manifestations have been reported in almost every organ, including the skin and the hematologic, cardiovascular, musculoskeletal, and nervous system due to direct local effects, after dissemination of bacteria or indirect effects. The correct identification of M. pneumoniae infections is vital for prescription of the appropriate therapy.There are scarce specific findings of clinical laboratory results for the diagnosis of M. pneumoniae infection. Detection of M. pneumoniae infections can be achieved using culture, serology, or molecular-based methods. Culture is time-consuming, laborious, and expensive. The major types of serological tests for M. pneumoniae include the microtiter plate enzyme immunoassay (EIA), the membrane EIA, indirect immunofluorescence, and particle agglutination. Nucleic acid amplification tests (NAATs) include traditional PCR, nested PCR, real-time quantitative PCR, nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP) technology, and RNA simultaneous amplification and testing (SAT). Macrolides have been the drug of choice for treating M. pneumoniae infection in past years. Clinically significant acquired macrolide-resistant M. pneumoniae (MRMP)has emerged worldwide which may be associated with more extrapulmonary complications, and severe clinical and radiological features. Since molecular-based assays can detect M. pnueumoniae in clinical specimens, there is a need for real point of care testing for fast detection of M. pneumoniae or its DNA and mutations in macrolide resistance gene. It is necessary to develop safe vaccines that provide protective immunity against M.pneumoniae infection.
Topics: Child; Humans; Mycoplasma pneumoniae; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Clinical Relevance; Macrolides; Drug Resistance, Bacterial; Real-Time Polymerase Chain Reaction
PubMed: 37741157
DOI: 10.1016/j.ijmmb.2023.100480 -
Pharmacotherapy Sep 2023To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real-world clinical practice among a...
STUDY OBJECTIVE
To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real-world clinical practice among a large US general population.
DESIGN
Retrospective cohort study design.
DATA SOURCE
MarketScan commercial and Medicare supplemental databases.
PATIENTS
Adults patients with at least one prescription fill for fluoroquinolone or macrolide antibiotics.
INTERVENTION
Fluoroquinolone or macrolide antibiotics.
MEASUREMENTS AND MAIN RESULTS
The primary outcome was estimated incidence of aortic aneurysm or dissection associated with the use of fluoroquinolones compared with macrolides during a 60-day follow-up period in a 1:1 propensity score-matched cohort. We identified 3,174,620 patients (1,587,310 in each group) after 1:1 propensity score matching. Crude incidence of aortic aneurysm or dissection was 1.9 cases per 1000 person-years among fluoroquinolone users and 1.2 cases per 1000 person-years among macrolide users. In multivariable Cox regression, compared with macrolides, the use of fluoroquinolones was associated with an increased risk of aortic aneurysm or dissection (aHR: 1.34; 95% CI: 1.17-1.54). The association was primarily driven by a high incidence of aortic aneurysm cases (95.8%). Results of sensitivity (e.g., fluoroquinolone exposure ranging from 7 to 14 days (aHR: 1.47; 95% CI: 1.26-1.71)) and subgroup analyses (e.g., ciprofloxacin (aHR: 1.26; 95% CI: 1.07-1.49) and levofloxacin (aHR: 1.44; 95% CI: 1.19-1.52)) remained consistent with main findings.
CONCLUSIONS
Fluoroquinolone use was associated with a 34% increased risk of aortic aneurysm or dissection compared with macrolide use among a general US population.
Topics: Adult; Humans; Aged; United States; Fluoroquinolones; Cohort Studies; Propensity Score; Retrospective Studies; Aortic Dissection; Medicare; Aortic Aneurysm; Anti-Bacterial Agents; Macrolides
PubMed: 37381584
DOI: 10.1002/phar.2841 -
Clinical Infectious Diseases : An... Feb 2024Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major... (Randomized Controlled Trial)
Randomized Controlled Trial
An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.
BACKGROUND
Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode.
METHODS
We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin.
RESULTS
Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI.
CONCLUSIONS
In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA.
CLINICAL TRIALS REGISTRATION
www.clinicaltrials.gov (NCT02692651).
Topics: Humans; Adolescent; Anti-Bacterial Agents; Vancomycin; Fidaxomicin; Clostridioides difficile; Aminoglycosides; Clostridium Infections; Diarrhea
PubMed: 37797310
DOI: 10.1093/cid/ciad606 -
Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.Chest Oct 2023Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M...
BACKGROUND
Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance.
RESEARCH QUESTION
Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease?
STUDY DESIGN AND METHODS
In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance.
RESULTS
Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%).
INTERPRETATION
In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT03038178; URL: www.
CLINICALTRIALS
gov.
Topics: Humans; Female; Middle Aged; Male; Amikacin; Anti-Bacterial Agents; Mycobacterium abscessus; Liposomes; Clofazimine; Azithromycin; Macrolides; Drug Resistance, Bacterial; Leprostatic Agents; Cystic Fibrosis; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests
PubMed: 37419144
DOI: 10.1016/j.chest.2023.05.036 -
International Journal of Antimicrobial... Sep 2023Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with... (Meta-Analysis)
Meta-Analysis Review
Respiratory fluoroquinolone monotherapy vs. β-lactam plus macrolide combination therapy for hospitalized adults with community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild-to-moderate community-acquired pneumonia (CAP). Efficacy of these regimens has not been adequately evaluated.
METHODS
A systematic review of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and β-lactam plus macrolide combination therapy in hospitalised adults with CAP was performed. A meta-analysis was performed using a random effects model. The primary outcome was clinical cure rate. Quality of evidence (QoE) was evaluated using GRADE methodology.
RESULTS
A total of 4140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (6 trials) were the predominant respiratory fluoroquinolones evaluated, and the β-lactam plus macrolide group used ceftriaxone plus a macrolide (10 trials), cefuroxime plus azithromycin (5 trials), and amoxicillin/clavulanate plus a macrolide (2 trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47; 95% confidence interval [95% CI: 1.17-1.83]; P = 0.0008; I = 0%; 17 RCTs; moderate QoE) and microbiological eradication rate (86.0% vs. 81.0%; OR 1.51 [95% CI: 1.00-2.26]; P = 0.05; I = 0%; 15 RCTs; moderate QoE) than patients receiving β-lactam plus macrolide combination therapy. All-cause mortality (7.2% vs. 7.7%; OR 0.88 [95% CI: 0.67-1.17]; I = 0%; low QoE) and adverse events (24.8% vs. 28.1%; OR 0.87 [95% CI: 0.69-1.09]; I = 0%; low QoE] were similar in the two groups.
CONCLUSION
Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiological eradication; however, it did not impact mortality.
Topics: Adult; Humans; beta-Lactams; Fluoroquinolones; Macrolides; Pneumonia, Bacterial; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Community-Acquired Infections
PubMed: 37385561
DOI: 10.1016/j.ijantimicag.2023.106905 -
The Lancet. Gastroenterology &... Jan 2024We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region.
METHODS
We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I. The study is registered in PROSPERO, CRD42022339956.
FINDINGS
A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I=96%) for clarithromycin, 52% (49-55; I=99%) for metronidazole, 26% (24-29; I=96%) for levofloxacin, 4% (3-5; I=95%) for tetracycline, and 4% (3-5; I=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I=93%) for clarithromycin, 61% (55-66; I=99%) for metronidazole, 35% (31-39; I=95%) for levofloxacin, 4% (2-6; I=96%) for tetracycline, and 6% (4-8; I=96%) for amoxicillin in the Asia-Pacific region.
INTERPRETATION
Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed.
FUNDING
Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Clarithromycin; Metronidazole; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Drug Resistance, Microbial; Asia
PubMed: 37972625
DOI: 10.1016/S2468-1253(23)00281-9 -
Chest Jan 2024There are several antibiotic regimens to treat community-acquired pneumonia (CAP). (Clinical Trial)
Clinical Trial
Comparative Effectiveness of First-Line and Alternative Antibiotic Regimens in Hospitalized Patients With Nonsevere Community-Acquired Pneumonia: A Multicenter Retrospective Cohort Study.
BACKGROUND
There are several antibiotic regimens to treat community-acquired pneumonia (CAP).
RESEARCH QUESTION
In patients hospitalized to a non-ICU ward setting with CAP, is there a difference between first-line and alternative antibiotic regimens (β-lactam plus macrolide [BL+M], β-lactam [BL] alone, respiratory fluoroquinolone [FQ], or β-lactam plus doxycycline [BL+D]) in terms of in-hospital mortality?
STUDY DESIGN AND METHODS
This retrospective cohort study included consecutive patients admitted with CAP at 19 Canadian hospitals from 2015 to 2021. Taking a target trial approach, patients were categorized into the four antibiotic groups based on the initial antibiotic treatment within 48 h of admission. Patients with severe CAP requiring ICU admission in the first 48 h were excluded. The primary outcome was all-cause in-hospital mortality. Secondary outcome included time to being discharged alive. Propensity score and overlap weighting were used to balance covariates.
RESULTS
Of 23,512 patients, 9,340 patients (39.7%) received BL+M, 9,146 (38.9%) received BL, 4,510 (19.2%) received FQ, and 516 (2.2%) received BL+D. The number of in-hospital deaths was 703 (7.5%) for the BL+M group, 888 (9.7%) for the BL group, 302 (6.7%) for the FQ group, and 31 (6.0%) for the BL+D group. The adjusted risk difference for in-hospital mortality when compared with BL+M was 1.5% (95% CI, -0.3% to 3.3%) for BL, -0.9% (95% CI, -2.9% to 1.1%) for FQ, and -1.9% (95% CI, -4.8% to 0.9%) for BL+D. Compared with BL+M, the subdistribution hazard ratio for being discharged alive was 0.90 (95% CI, 0.84-0.96) for BL, 1.07 (95% CI, 0.99-1.16) for FQ, and 1.04 (95% CI, 0.93-1.17) for BL+D.
INTERPRETATION
BL+M, FQ, and BL+D had similar outcomes and can be considered effective regimens for nonsevere CAP. Compared with BL+M, BL was associated with longer time to discharge and the CI for mortality cannot exclude a small but clinically important increase in risk.
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Canada; Community-Acquired Infections; Drug Therapy, Combination; Length of Stay; Macrolides; Pneumonia; Retrospective Studies
PubMed: 37574164
DOI: 10.1016/j.chest.2023.08.008