The medical journal "Health of Ukraine. Surgery, Orthopedics, Traumatology, Intensive Care" No. 5, 2020, published the second part of an article by I. Bereznyakov, MD, Professor, Head of the Department of Therapy at the Kharkiv Medical Academy of Postgraduate Education, and President of the Ukrainian Association for the Rational Use of Antibiotics. The article focuses on the state of antibiotic resistance in Ukraine based on the results of the AURA study. The key points from the first part are presented in the publication: Antibiotic Resistance in Ukraine Based on the Results of the AURA Study (Part 1)

AURA is the first and only monitoring of antibiotic resistance in Ukraine over the past decade. The AURA study includes an analysis of the susceptibility of 800 microbial isolates to 23 antimicrobial agents and was conducted using EUCAST criteria for interpreting the results.

I. Bereznyakov compares the obtained data on the spread of antibiotic resistance in Ukraine with those in other European countries, although it should be noted that the AURA study analyzed strains obtained from wounds associated with skin and soft tissue infections, intra-abdominal infections, and bone and joint infections, while the European Antimicrobial Resistance Surveillance Network (EARS-Net) only considers isolates from blood and cerebrospinal fluid. In Europe, there is a clear trend toward increasing prevalence of antibiotic resistance in clinically significant bacteria from north to south and from west to east.

Staphylococcus spp . EARS-Net tracks only methicillin-resistant Staphylococcus aureus (MRSA) strains. The situation in Ukraine is similar to that in Hungary and Slovakia, worse than in Poland, and better than in Romania. However, the prevalence of MRSA in different healthcare facilities in Ukraine varies widely. According to the AURA study, the proportion of methicillin-susceptible staphylococci (MSSA) is 65% among all staphylococci, and 72.8% among S. aureus (monotherapy is the most effective treatment for MSSA infections, and β-lactams remain the drugs of choice). The proportion of MRSA among all Staphylococcus spp. is 35%, and among S. aureus – 27.2%. Almost all S. haemolitycus and S. epidermidis isolates were methicillin-resistant. If an antibiotic active against MRSA must be prescribed, a choice should be made between teicoplanin and linezolid. Tetracycline, aminoglycosides, macrolides, and lincosamides should not be used empirically for MRSA infections. Decreased susceptibility of MRSA to vancomycin is a concerning development.

Enterococcus spp. In Ukraine, Enterococcus faecalis and Enterococcus faecium remain almost 100% susceptible to vancomycin, linezolid, and tigecycline. Teicoplanin and fosfomycin are reliable agents for treating infections caused by E. faecalis , with fosfomycin sensitivity remaining even in vancomycin-resistant enterococci. Vancomycin, linezolid, and tigecycline are preferred for treating infections caused by E. faecium .

Streptococcus spp. In Ukraine, streptococci maintain high susceptibility (90%) to β-lactam antibiotics, which remain the drugs of choice for the treatment of streptococcal infections. If necessary, numerous non-β-lactam alternatives (e.g., co-trimoxazole) are available, with susceptibility rates that may be even higher. However, monotherapy for streptococcal infections with levofloxacin, macrolides, lincosamides, and tetracycline is associated with a high risk of clinical failure due to the spread of resistance to these antibiotics.

Escherichia coli. Carbapenem resistance in E. coli is a serious problem: in Ukraine, it has reached 8.5%, while in the EU/EEP countries, it is absent or <1%. E. coli remains the most common cause of bloodstream infections, and carbapenem-resistant Enterobacteriaceae are rapidly spreading and associated with high mortality. In Ukraine, the highest susceptibility of E. coli remains to carbapenems (meropenem, ertapenem), nitrofurantoin, colistin, fosfomycin, and cefoperazone/sulbactam. Among aminoglycosides, the highest susceptibility of E. coli is to gentamicin. Due to the low sensitivity of E. coli to fluoroquinolones, the latter should not be considered either as monotherapy or as a component of combination antibiotic therapy for infections of the skin and soft tissues, bones and joints, and intra-abdominal infections caused by these microorganisms.

Klebsiella spp. The most significant species is Klebsiella pneumoniae , which produces chromosomal class A β-lactamases and is therefore naturally resistant to aminopenicillins. In Ukraine, 41.7% of Klebsiella spp. produce extended-spectrum β-lactamases (ESBL). Carbapenems are often resistant to ESBL and have been a treatment option for severe infections caused by K. pneumoniae , but carbapenem resistance continues to spread. While carbapenem monotherapy is effective against K. pneumoniae in Hungary, Slovakia, and Poland, this is no longer the case in Ukraine and Romania. Colistin remains the only antibiotic to which Klebsiella remains sensitive in Ukraine. Klebsiella spp. susceptibility to fosfomycin and meropenem ranges from 75-80%. An option for treating infections caused by Klebsiella spp. is combination antibiotic therapy using the listed antibiotics and, possibly, aminoglycosides (primarily amikacin and gentamicin).

Proteus spp. , whether ESBL-producing or non-ESBL-producing, retain high susceptibility (97-100%) to meropenem, piperacillin/tazobactam, and cefoperazone/sulbactam. Almost a third (30.8%) of Proteus spp. strains produced ESBL, which limits the empirical use of unprotected third-generation cephalosporins (ceftazidime).

Pseudomonas aeruginosa is naturally resistant to many antibiotics. Furthermore, the prevalence of antibiotic resistance among P. aeruginosa in Ukraine is worse than in neighboring EU countries, and significantly worse across all tested antibiotics. The only antibiotic to which P. aeruginosa maintains high susceptibility (93.3%) in Ukraine is colistin. For empirical treatment of infections caused by P. aeruginosa , combination antibiotics should be used.

Acinetobacter spp. Like Pseudomonas aeruginosa, Acinetobacter spp. (primarily those in the A. baumannii complex) are naturally resistant to many antibiotics. In Ukraine, very high susceptibility to Acinetobacter spp. remains only to colistin. The susceptibility rate of Acinetobacter spp. does not reach 40% to any other antibiotic. The situation is similar in neighboring EU countries. For empirical treatment of infections caused by bacteria in the A. baumannii complex, combination antibiotics should be used.