Survival benefit associated with clarithromycin in severe community-acquired pneumonia: A matched comparator study

Kyriazopoulou, Evdoxia; Sinapidis, Dimitrios; Halvatzis, Stamatios; Velissaris, Dimitrios; Alexiou, Nikolaos; Kosmas, Vasilios; Adami, Maria‐Evangelia; Kyprianou, Miltiades; Kyprianou, Aikaterini; Stefos, Aggelos; Lada, Malvina; Koutoukas, Pantelis; Pavlaki, Maria; Kyriakoudi, Anna; Makina, Anna; Gogos, Charalambos; Niederman, Michael S.; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1016/j.ijantimicag.2019.10.017

Cited by 14 publications

(12 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on previous experience with clarithromycin [9-12], we sought to investigate its potential in reducing the hyper-inflammatory response in moderate COVID-19 and contribute to better clinical outcomes than currently available treatment approaches. Analysis revealed that clarithromycin treatment was associated with a significantly greater clinical benefit at the EOT visit of 86.7%, as compared with 73.3% achieved by the concurrent SOC comparators.…”

Section: Discussionmentioning

confidence: 99%

Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

Tsiakos

Tsakiris²,

Tsibris³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundClarithromycin clinical efficacy has not been described in COVID-19.Research questionIs oral clarithromycin beneficial for treating patients diagnosed with COVID-19?Study and methodsAn open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted at four study sites in Greece between May and October 2020. Ninety participants with respiratory tract infections received clarithromycin 500 mg every 12 hours for 7 days; another 90 standard-of-care (SOC) propensity score-matched concurrent controls received azithromycin plus hydroxychloroquine. The composite primary endpoint was defined for patients with upper respiratory tract infection as: (a) no need for hospital re-admission or (b) lack of progression into lower respiratory tract infection and, for patients with lower respiratory tract infection, as at least 50% decrease of the score of respiratory symptoms at the end-of-treatment (EOT) without progression into severe respiratory failure (SRF). The incidence SRF at the test-of-cure (TOC) on day 14 was a secondary endpoint. For clarithromycin-treated patients, viral load of SARS-CoV-2, biomarkers, the function of mononuclear cells, and safety were assessed; biomarkers were also measured in SOC comparators.ResultsThe primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%) and 73.3% of concurrent SOC comparators (95%CIs; 63.4-81.4%). The odds ratio for the primary endpoint with clarithromycin treatment in univariate analysis was 2.36 (95%CIs 1.09-5.08; P: 0.039). Results were confirmed after multivariate stepwise logistic regression analysis (odds ratio 3.30; 95% CI 1.10-9.87; P: 0.033). At the TOC visit, the incidence of SRF was 12.2% (n = 11 ; 95%CIs 6.9-20.6%) among patients treated with clarithromycin (odds ratio for SRF 0.38; 95%CIs 0.17-0.84) versus 26.7% (n= 24; 95%CIs 18.6-36.6%) among concurrent SOC comparators (P: 0.023). Clarithromycin use was associated with decreases in circulating levels of C-reactive protein, of tumour necrosis factor-alpha and of interleukin (IL)-6; by an increase of the ratio of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 relative viral load. No safety concerns were reported. Patients starting clarithromycin with the first five days from symptoms onset achieved better responses.InterpretationClarithromycin treatment is associated with early clinical improvement in patients with moderate COVID-19. Modulation of the Th1/Th2 responses is proposed as the mechanism of action.Trial RegistrationClinicalTrials.gov, NCT04398004

show abstract

Section: Discussionmentioning

confidence: 99%

Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

Tsiakos

Tsakiris²,

Tsibris³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…One of the studies is a retrospective analysis of prospectively collected data from the HSSG. The aim of this study was not to refer to the macrolide group of antibiotics in general but to run a direct comparison of the treatment outcomes of a combination of β-lactam with clarithromycin to the combination of β-lactam and azithromycin [ 4 ]. Analysed patients had sepsis according to the Sepsis-3 definitions and comparisons to patients treated with monotherapies either with β-lactams or with moxifloxacin/levofloxacin were done.…”

Section: Positionmentioning

confidence: 99%

“…A synopsis of these eight clinical studies is provided in Table 1. All studies were conducted among patients hospitalized with CAP [4][5][6][7][8][9][10][11].…”

Section: Macrolides Have a Major Adjunctive Role And Should Always Be Included In The Starting Treatment Regimen Of Cap Requiring Hospitamentioning

confidence: 99%

“…The Hellenic Sepsis Study Group (HSSG) ( www.sepsis.gr ) has published four booklets in the years 2008, 2011, 2014 and 2017 for the management of sepsis where the intravenous use of clarithromycin has been suggested not only for the management of CAP but also for severe sepsis by Gram-negative bacteria based on evidence coming from two randomized clinical trials (RCTs) conducted in Greek populations [ 2 , 3 ]. This position of the HSSG alongside recent evidence for the salient importance of adjunctive clarithromycin therapy in CAP [ 4 ] prompted the generation of this position paper for the role of macrolides in the empirical treatment of CAP coming from four scientific societies of Greece.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Macrolides for the Management of Community-Acquired Pneumonia and Pneumonia by the Novel Coronavirus SARS-CoV-2 (COVID-19): A Position Paper by Four Medical Societies from Greece

Giamarellos‐Bourboulis

Daikos

Gargalianos³

et al. 2021

Infect Dis Ther

Self Cite

View full text Add to dashboard Cite

In light of the accumulating evidence for survival benefit coming from the use of macrolides for community-acquired pneumonia (CAP), a group of experts from the field of internal medicine and infectious diseases frame a position statement on the use of macrolides for the management of bacterial CAP and for infection by the novel coronavirus (COVID-19). The statement is framed taking into consideration existing publications and own research experience. The main content of this statement is that the combination of one β-lactam and a macrolide should be the first treatment of choice for patients with severe bacterial CAP. Severity is assessed as scoring 2 or more points on the CURB65 scoring system of severity or as pneumonia severity index III to V or C-reactive protein more than 150 mg/l; the suggested macrolide is either azithromycin or clarithromycin. The experts also suggest that in COVID-19 pneumonia, the combination of one β-lactam and a macrolide should be reserved only when there is strong suspicion of bacterial co-infection.

show abstract

“…Clarithromycin is a macrolide antibiotic that has been widely used as a monotherapy for bacterial respiratory infectious diseases. Clarithromycin has also been used as a standard combination therapy with beta-lactam antibiotics for severe communityacquired pneumonia 8 , owing to its ability to suppress inflammatory cytokines during these critical cases. Viral respiratory diseases, such as influenza, are not an exception in the mechanism of exacerbation, and combination therapy with clarithromycin and antiviral agents showed clinical efficacy in influenza A infection 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of clarithromycin on COVID-19 pneumonia without oxygen administration; protocol for multicenter, open-label, randomized-controlled, 3-armed parallel group comparison, exploratory trial (CAME COVID study)

Yamamoto

Hosogaya

Sakamoto

et al. 2021

Preprint

View full text Add to dashboard Cite

Introduction: The coronavirus disease 2019 (COVID-19) epidemic has been emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, no treatment strategy has been established for mild COVID-19 patients who do not require oxygen administration. The spread of SARS-CoV-2 has been mostly through patients with mild COVID-19; therefore, treating patients with mild COVID-19 is critical in society. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza infection. In this study, we aimed to evaluate the efficacy of clarithromycin in patients with mild COVID-19. Methods and analysis: This is a multicenter, open-label, randomized controlled, 3-armed parallel group comparison, exploratory trial. Subjects with mild COVID-19 pneumonia who did not require oxygen administration were enrolled and randomly assigned in a 1:1:1 ratio to Group A (administration of clarithromycin 800 mg/day), Group B (administration of clarithromycin 400 mg/day), or Group C (standard treatment without clarithromycin). The primary endpoint was the number of days required to improve clinical symptoms as measured by the severity score. Secondary endpoints included days to recover the body temperature, proportion of subjects with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers, and pneumonia infiltrations. Ethics and dissemination: The study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all participants. The results of this study will be reported as journal publications. Registration: This study was registered at the Japan Registry of Clinical Trials (registration number: jRCTs071210011).

show abstract

Survival benefit associated with clarithromycin in severe community-acquired pneumonia: A matched comparator study

Cited by 14 publications

References 21 publications

Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

The Role of Macrolides for the Management of Community-Acquired Pneumonia and Pneumonia by the Novel Coronavirus SARS-CoV-2 (COVID-19): A Position Paper by Four Medical Societies from Greece

Efficacy of clarithromycin on COVID-19 pneumonia without oxygen administration; protocol for multicenter, open-label, randomized-controlled, 3-armed parallel group comparison, exploratory trial (CAME COVID study)

Contact Info

Product

Resources

About