Antibiotic therapy for orthopedic infections caused by gram-negative pathogens over a 12-year observation period

Introduction Treatment of patients with orthopedic infection includes a combination of the optimal surgical debridement and  adequate antibacterial therapy. Gram-negative bacteria are encountered in 13–28 % of orthopedic infections, and A. baumannii, K. pneumoniae, P. aeruginosa are significant bacteria notorious for its high and intrinsic antibiotic resistance and can be associated with worse outcomes.

The objective was to substantiate the choice of drug for targeted empirical and etiotropic antibacterial therapy based on the analysis of antibiotic resistance in leading gram-negative bacteria (A. baumannii, K. pneumoniae, P. aeruginosa) isolated from patients with orthopedic infection.

Material and methods Antibiotic sensitivity of leading Gram(–) microorganisms isolated from patients with  orthopedic infection was retrospectively examined between 01.01.2011 and 31.12.2022. The average frequency of isolated resistant strains was examined and resistance trends of leading Gram(–) pathogens to various antimicrobialbacterial drugs (fluoroquinolones, co-trimoxazole, cephalosporins, carbapenems, monobactams, aminoglycosides, fosfomycin, colistin) determined.

Results Over a 12-year period, statistically significant trends were revealed towards an increase in the proportion of A. baumannii strains resistant to ciprofloxacin (p = 0.024) and levofloxacin (p = 0.012), and P. aeruginosa (p = 0.018) and K. pneumoniae (p = 0.018) strains resistant to ciprofloxacin. The predicted proportion of A. baumannii strains resistant to fluoroquinolones tends to 100 %. There was a significant increase in A. baumannii and P. aeruginosa strains resistant to cefoperazone+[sulbactam] (p = 0.027 and p = 0.010, respectively), K. pneumoniae strains resistant to meropenem and imipenem (p = 0.037 and p = 0.003, respectively), and P. aeruginosa strains resistant to imipenem (p = 0.001). No statistically significant trends were found for the remaining antibiotics; drug resistance of the pathogens remained stable or had a wave-like course over the 12-year period. Cefoperazone + [sulbactam] was the optimal drug active against Gram(–) bacteria.

Discussion There is an authoritative list of antimicrobiall drugs active against A. baumannii, K. pneumoniae, P. aeruginosa strains, mainly containing drugs for parenteral administration. The list is limited to one or two groups for resistant strains, and there are no drugs available in oral form. This causes difficulties in the infection control and a high rate of relapses. The negative dynamics in increasing antibiotic resistance of leading Gram(–) pathogens to fluoroquinolones, cephalosporins and carbapenems is a global problem necessitating the use of reserve antibiotics.

Conclusion Protected cephalosporin is more practical for targeted empirical initial antimicrobial therapy due to the lower risk of selected resistant strains. Fluoroquinolones and carbapenems can be used with the sensitivity known. Polymyxin B and fosfomycin should be considered as reserve drugs for the treatment of infections caused by strains resistant to other AB, and prescribed as part of combination therapy. Aminoglycosides and unprotected cephalosporins can be an alternative due to the pharmacokinetic characteristics and high level of resistance when more active drugs cannot be administered.characteristics and high level of resistance when more active drugs cannot be administered.

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