Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study

Efthymia Giannitsioti; Mauro José Salles; Andreas Mavrogenis; Dolors Rodriguez-Pardo; Ibai Los-Arcos; Alba Ribera; Javier Ariza; María Dolores Del Toro; Sophie Nguyen; Eric Senneville; Eric Bonnet; Monica Chan; Maria Bruna Pasticci; Sabine Petersdorf; Natividad Benito; Nuala O' Connell; Antonio Blanco García; Gábor Skaliczki; Pierre Tattevin; Zeliha Kocak Tufan; Nikolaos Pantazis; Panayiotis D Megaloikonomos; Panayiotis Papagelopoulos; Alejandro Soriano; Antonios Papadopoulos; The Esgiai Collaborators Study Group

doi:10.5194/jbji-7-279-2022

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study

J Bone Jt Infect. 2022 Dec 21;7(6):279-288. doi: 10.5194/jbji-7-279-2022. eCollection 2022.

Authors

Efthymia Giannitsioti¹, Mauro José Salles², Andreas Mavrogenis³, Dolors Rodriguez-Pardo⁴, Ibai Los-Arcos⁴, Alba Ribera⁵, Javier Ariza⁵, María Dolores Del Toro⁶, Sophie Nguyen⁷, Eric Senneville⁷, Eric Bonnet⁸, Monica Chan⁹, Maria Bruna Pasticci¹⁰, Sabine Petersdorf¹¹, Natividad Benito¹², Nuala O' Connell¹³, Antonio Blanco García¹⁴, Gábor Skaliczki¹⁵, Pierre Tattevin¹⁶, Zeliha Kocak Tufan¹⁷, Nikolaos Pantazis¹⁸, Panayiotis D Megaloikonomos³, Panayiotis Papagelopoulos³, Alejandro Soriano¹⁹, Antonios Papadopoulos¹, The Esgiai Collaborators Study Group²⁰

Affiliations

¹ Fourth Department of Internal Medicine, University General Hospital Attikon, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
² Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
³ First Department of Orthopaedics, University General Hospital Attikon, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
⁴ Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁵ Department of Infectious Diseases, Hospital Universitari Bellvitge, Barcelona, Spain.
⁶ Infectious Diseases Unit, Hospital Universitario Virgen Macarena, Instituto de Biomedicina de Sevilla (IBIS), Universidad de Sevilla, Seville, Spain.
⁷ Infectious Diseases Department, Gustave Dron Hospital, Tourcoing, France.
⁸ Department of Infectious Diseases, Clinique Pasteur, Toulouse, France.
⁹ Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore.
¹⁰ Infectious Diseases Unit, University of Perugia, Perugia, Italy.
¹¹ Institute for Medical Laboratory Diagnostics, Helios University Clinic Wuppertal, Wuppertal, Germany.
¹² Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹³ Department of Clinical Microbiology, University Hospital Limerick, Limerick, Ireland.
¹⁴ Bone and Joint Infection Unit, Department of Emergency Medicine, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain.
¹⁵ Department of Orthopaedics, Semmelweis University, Budapest, Hungary.
¹⁶ Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France.
¹⁷ Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Yildirim Beyazit University, Ankara Atatürk Education and Research Hospital, Ankara, Turkey.
¹⁸ Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹⁹ Department of Infectious Diseases, Hospital Clínic, Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain.
²⁰ A full list of authors appears at the end of the paper.

Abstract

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( $n = 57$ ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( $n = 16$ ), Pseudomonas aeruginosa ( $n = 14$ ; XDR 50 %), Klebsiella spp. ( $n = 7$ ), Enterobacter spp. ( $n = 9$ ), Acinetobacter spp. ( $n = 5$ ), Proteus mirabilis ( $n = 3$ ), Serratia marcescens ( $n = 2$ ) and Stenotrophomonas maltophilia ( $n = 1$ ). The prevalence of ESBL (extended-spectrum $β$ -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( $n = 37$ ; 64.9 %) were treated with a combination including carbapenems ( $n = 32$ ) and colistin ( $n = 11$ ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( $p = 0.008$ ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age $> 60$ years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; $p = 0.004$ ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; $p = 0.024$ ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.