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

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 $\beta$ -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.

Figure 1

Remission of OAI split by (a) type of surgical treatment or (b) type of antimicrobial resistance.

Figure 2

Kaplan–Meier survival plot of remission of OAI the lower limbs by MDR/XDR GNB (log rank $x^{\mathrm{2}}=\mathrm{7.919}$ , DF  $=$  1, $p=\mathrm{0.005}$ ).