Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

Dinh, Aurélien; Ropers, Jacques; Duran, Clara; Davido, Benjamin; Deconinck, Laurène; Matt, Morgan; Sénard, Olivia; Lagrange, A.; Makhloufi, S.; Mellon, Guillaume; Lastours, Victoire de; Bouchand, Frédérique; Mathieu, Emmanuel; Kahn, Jean‐Emmanuel; Rouveix, É.; Grenet, J.; Dumoulin, Jennifer; Chinet, Thierry; Pépin, Marion; Delcey, Véronique; Diamantis, S.; Benhamou, D.; Vitrat, Virginie; Dombret, Marie-Christine; Renaud, Bertrand; Perronne, Christian; Claessens, Yann-Érick; Labarère, José; Bédos, Jean‐Pierre; Aegerter, Philippe; Crémieux, Anne‐Claude; Attal-Behar, Julie; Beaune, Sébastien; Cudennec, Tristan; Laroche, M. de; Thézy, Albane de; Dupont, Caroline; Fercot, Élise; Giraut, Violaine; Greffe, S.; Guyot, Caroline; Labrune, Sylvie; Lachâtre, Marie; Moulias, Sophie; Naline, Charlotte; Sahut-D’Izarn, Marine; Sefssafi, Abel; Teillet, Laurent; Bru, J.P.; Gaillat, J.; Gautier, Vincent; Janßen, C.; Pagani, Léonardo; Abderrahmane, Malika; Camuset, Juliette; Legall, C.; Longuet-Flandres, Pascale; Menn, Anne-Marie; Lecronier, Marie; Prevost, Gwenolée; Burdet, Charles; Derradji, Ouda; Escaut, L.; Hinglais, E.; Lebras, P; Lefèvre, Édouard; Noaillon, Mathilde; Rabier, Pauline; Raphaël, Maurice; Teicher, Elina; Verny, Christiane; Vittecoq, D.; Wyplosz, Benjamin; Hayoun, M. Ben; Brun‐Vézinet, Françoise; Casalino, Enrique; Choquet, Christophe; Duval, Xavier; Houhou, Nadhira; Joly, Véronique; Lescure, Xavier; Pogliaghi, Manuela; Rioux, C.; Yazdanpanah, Yazdan; Barros, Elsa Maria da Silva; Begga, Belinda; Boukobza, Sébastien; Bouredji, Houria; Chouahi, Imad; Delacroix, Isabelle; Froissart, Antoine; Garrait, Valérie; Ngwem, Elsa; Phlippoteau, Catherine; Salehabadi, Sepehr; Toper, C.; Viñas, F.; Amsilli, M.; Épaulard, Olivier; Pavèse, Patricia; Isabelle, Pierre; Stahl, Jean-Paul; Aulagnier, Jérôme; Celerier, Julie; Cojocariu, Roxana; Rachline, Charlotte; Schoindre, Y.; Sene, Thomas; Thierry, Christelle; Aparicio, C.; Lopes, Amanda; Morgand, Marjolaine; Sellier, Pierre; Simoneau, Guy G.; Chakvetadze, Catherine; Gauthier, Arnaud; Jidar, Kaoutar; Jourdain, Béatrice; Boitiaux, J.F.; Deschamps, Patrick; Devaud, Edouard; Philippe, B.; Calin, Ruxandra-Oana; Chroboczek, Tomasz; Truchis, Pierre de; Chapuzet, C.; Chauffrey, Laure; Etienne, Manuel; Joly, Luc‐Marie; Obstoy, Bérengère; Salaün, Mathieu; Thiberville, Luc; Tillon, J.; Bollens, Diane; Bottéro, J.; Campa, Pauline; Cosquéric, Gaëlle; Lefebvre, Bénédicte; Ouazene, Zineb; Pacanowski, Jérôme; Pateron, Dominique; Valin, Nadia; Compain, Caroline; Cordel, Hugues; Doumenc, Benoît; Foïs, Eléna; Gambier, Nicolas; Khuong, M. A.; Pasqualoni, E.; Poupard, Marie

doi:10.1016/s0140-6736(21)00313-5

Cited by 108 publications

(51 citation statements)

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“…The study design and main results have been published previously. 16 In brief, patients who met the following inclusion criteria were studied: age of 18 years or older, hospitalized in a non-critical care ward for CAP, treated with β-lactams, chosen at the discretion of the physician in charge to receive amoxicillin-clavulanate (oral or intravenous) or parenteral thirdgeneration cephalosporin (ceftriaxone or cefotaxime), and presented after 72 hours of treatment with a clinical response defined by the presence of stability criteria. 3 Race and ethnicity data are not allowed to be collected in France for research by law; therefore, these data are not available for analysis.…”

Section: Study Design Sites and Study Populationmentioning

confidence: 99%

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia

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Section: Study Design Sites and Study Populationmentioning

confidence: 99%

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia

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“…We assessed 38 full-text records for eligibility and included 11 eligible studies. (Fig1) Of these, 8 were published, [11][12][13][14][15][36][37][38] 1 was unpublished 39 and 2 studies were still ongoing, 40,41 resulting in 9 trials for the primary outcome analysis. The lists of included and excluded studies are provided in the appendix (eAppendix4 and 5).…”

Section: Resultsmentioning

confidence: 99%

“…[4][5][6] Our results suggest that an even shorter duration (3-5 days) may be considered, which is in line with the trials that found 3-day treatment was non-inferior to 8-day treatment. 12,37…”

Section: Discussionmentioning

confidence: 99%

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

Furukawa

Luo

Funada

et al. 2021

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ImportanceCommunity-acquired pneumonia (CAP) is a leading cause of morbidity and mortality globally. The optimal duration of antimicrobial therapy remains unclear and controversial.ObjectiveTo find the optimal treatment duration with antibiotics for CAP in adults.Data SourcesMEDLINE, Embase and CENTRAL from inception to present (25 August, 2021).Study SelectionAll randomized controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. We included any antibiotics, administered orally or intravenously. We included both outpatients and inpatients but not those admitted to intensive care unit.Data Extraction and SynthesisTwo review authors independently screened and extracted data. We conducted random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the pre-specified non-inferiority margin of 10% examined against 10 days using intention-to-treat dataset.Main Outcomes and MeasuresThe primary outcome was clinical improvement at day 15 (range 7-45 days). Secondary outcomes were all-cause mortality, serious adverse events, and clinical improvement at day 30 (15-60 days). We calculated odds ratios.ResultsWe included 9 trials (2399 patients with a mean [SD] age of 61.2 [22.1]; 39% women). The duration-effect curve was monotonic with longer duration leading to lower probability of improvement, and the lower 95%CI curve was constantly above the prespecified non-inferiority margin throughout the examined duration. Harmful outcome curves indicated no association. The average percentage of clinical improvement rate at day 15 in the 10-day treatment arms was 68%. Using that average, we computed the absolute clinical improvement rates at the following durations: a 3-day treatment 75% (95%CI: 68 to 81%), 5-day treatment 72% (66 to 78%), and 7-day treatment 69% (61 to 76%).Conclusions and RelevanceShorter treatment duration probably achieves the optimal balance between efficacy and treatment burden for treating CAP in adults. However, the small number of included studies and the overall moderate to high risk of bias may compromise the certainty of the results. Further research focusing on the shorter duration range is required.RegistrationPROSPERO (CRD 42021273357).KEY POINTSQuestionWhat is the optimal treatment duration of antibiotics for community-acquired pneumonia (CAP) in adults.?FindingsThis systematic review and duration-effect meta-analysis of 9 trials with 2399 patients found that the shorter treatment duration (3-9 days) was likely to be non-inferior to the standard treatment duration (10 days) for CAP in adults if they achieved clinical stability.MeaningShorter antibiotic treatment duration probably achieves the optimal balance between efficacy and treatment burden for CAP in adults.

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“…In addition, the association of prolonged antimicrobial therapy with a differential outcome than a shorter duration of antibiotic treatment was not supported in literature [ 23 ]. As an example, shortened antibiotic duration (3 days) in patients (including older patients) with stability criteria during acute pneumonia was non-inferior to 8 days of treatment [ 24 ]. It could be insightful to evaluate the interest of EC in future studies to guide the duration of antimicrobial therapy and discontinue it as soon as a patient recovers from eosinopenia.…”

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confidence: 99%

Persistent eosinopenia is associated with in-hospital mortality among older patients: unexpected prognostic value of a revisited biomarker

et al. 2021

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Introduction Infection is one of the major causes of mortality and morbidity in older adults. Available biomarkers are not associated with prognosis in older patients. This study aimed to analyze the value of eosinopenia (eosinophil count< 100/mm3) as a prognosis marker among older patients with suspected or confirmed bacterial infection. Methods A retrospective study was performed from 1 January to 31 December 2018 among patients in a geriatrics ward suffering from a bacterial infection treated with antibiotics. Biomarker data including the eosinophil count, neutrophil count and C-reactive protein (CRP) were collected within 4 days after patient diagnosis. Persistent eosinopenia was defined as a consistent eosinophil count< 100/mm3 between Day 2 and Day 4. The association of biomarkers with 30-day hospital mortality in a multivariate analysis was assessed and their predictive ability using the area under the ROC curve (AUC) was compared. Results Our study included 197 patients with a mean age of 90 ± 6 years. A total of 36 patients (18%) died during their stay in hospital. The patients who died were more likely to have persistent eosinopenia in comparison to survivors (78% versus 34%, p < 0.001). In the multivariate analysis, persistent eosinopenia was associated with in-hospital mortality with an adjusted HR of 8.90 (95%CI 3.46–22.9). The AUC for eosinophil count, CRP and neutrophil count between Day 2 and Day 4 were 0.7650, 0.7130, and 0.698, respectively. Conclusion Persistent eosinopenia within 4 days of diagnosis of bacterial infection appeared to be a predictor of in-hospital mortality in older patients.

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Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

Cited by 108 publications

References 28 publications

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis

Persistent eosinopenia is associated with in-hospital mortality among older patients: unexpected prognostic value of a revisited biomarker

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