Russian

First RosNet report on antibiotic resistance in Russia

The data given below is the first RosNet report on antibiotic resistance in different bacterial species and genera in Russia. It includes both the results of RosNet projects and other well-standardized studies available. For convenience sake, community and nosocomial bacteria are presented separately.

Community Pathogens

Streptococcus pneumoniae

Recent survey of S.pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centers (Moscow, Smolensk and Yartsevo) showed that 7.5% pneumococci were intermediate-resistant to penicillin G (MIC 0.12-1 mg/L). There were no highly penicillin-resistant (MIC >2 mg/L) strains found, and amoxicillin/clavulanate was active against all penicillin non-susceptible isolates. Macrolide resistance level was 4.6%. The highest rate of resistance was proved to be to trimethoprim/sulfamethoxazole - 56.8%.

According to the preliminary data of «PeHAS-1» Project the frequency of penicillin-intermediate and -resistant S.pneumoniae was 9% and 0%, respectively. About 4% of pneumococci were erythromycin-resistant. Resistance to tetracycline and trimethoprim/sulfamethoxazole was observed quite commonly reaching 64.9% and 62.2%, respectively.

Streptococcus pyogenes

S.pyogenes remain uniformly highly susceptible to beta-lactam antibiotics. Resistance to macrolide antibiotics was recorded in 12.6% of clinical strains of S.pyogenes (Table 1). Whereas, high rate of tetracycline resistance (over 60%) is of great clinical importance.

Table 1. Antibiotic susceptibility of S.pyogenes (Smolensk, 1997)

Haemophilus influenzae

The data obtained from the survey in Moscow, Smolensk and Yartsevo showed that the prevalence of ampicillin-resistant H.influenzae was relatively low in 1998 (Table 2). The susceptibility to trimethoprim/sulfamethoxazole is of great concern since over 20% of the isolates were resistant.

Table 2. Antibiotic susceptibility of H.influenzae (1998)

Neisseria gonorrhoeae

Susceptibility testing of gonococci requires a special medium, which is quite expensive and not easily available in Russia. Thus data on antimicrobial susceptibility of gonococci is scarce and somewhat unreliable in Russia. The pilot study conducted in Smolensk (1999) proved that 77.9% of N.gonorrhoeae were resistant to penicillin, 96.1% - to doxicycline, and 1.3% were ciprofloxacin-intermediate. All tested strains were susceptible to ceftriaxone.

Escherichia coli

First multicenter (Moscow, Smolensk, Novosibirsk) study of antibiotic susceptibility of Gram(-) pathogens isolated from women with community-acquired acute and recurrent cystitis was conducted in 1998. E.coli was the most common causative agent. The highest frequency of resistance was observed to ampicillin (33.3%) and trimethoprim/sulfamethoxazole (18.4%) (Figure 1). While fluoroquinolones (norfloxacin and ciprofloxacin) proved to be the most active antimicrobials tested.

Figure 1. Antibiotic resistance (%) of E.coli (1998) AMP - ampicillin; GEN - gentamicin; TSX - trimethoptrim/sulfamethoxazole; NFT - nitrofurantoin; NAL - nalidixic acid; NOR - norfloxacin; CIP - ciprofloxacin.

Shigella flexneri and Shigella sonnei

Antibiotic susceptibility was determined in Shigella spp. strains isolated in Smolensk region during 1998-1999. Almost all S.flexneri strains collected in 1998 were resistant to ampicillin (95%), ampicillin/sulbactam (95%), trimethoprim/sulfamethoxazole (98%), chloramphenicol (98%), and tetracycline (98%). Whereas S.sonnei obtained during the same period were relatively less resistant to ampicillin (7%) with similar resistance rates to other antibiotics tested: trimethoprim/sulfamethoxazole - 100%, chloramphenicol - 72%, tetracycline - 93%. All Shigella isolates were susceptible to nalidixic acid and ciprofloxacin.

Susceptibility testing results for Shigella spp. isolated in 1999 in Moscow and Smolensk are given in Table 3. They indicate that no significant changes in S.flexneri susceptibility occurred, while resistance of S.sonnei to ampicillin and ampicillin/sulbactam increased from 7% in 1998 to 35% in 1999.

Table 3. Resistance (%) of Shigella spp. to antimicrobials (Moscow and Smolensk, 1999)

The data from Ekaterinburg (Table 4) also show that S.sonnei were less resistant to penicillins and tetracycline comparing to S.flexneri, with one exception - trimethoprim/sulfamethoxazole that was less active against S.sonnei. Note that about 4-5% of Shigella were resistant to ciprofloxacin.

Table 4. Resistance (%) of Shigella spp. to antimicrobials (Ekaterinburg, 1999)

Salmonella spp.

The results presented in Table 5 show that resistance to antimicrobial agents is rather low in Salmonella: 10% to tetracycline, 9.5% to chloramphenicol, and no cefotaxime-, ciprofloxacin- and trimethoprim/sulfamethoxazole-resistant isolates were found.

Table 5. Resistance (%) of Salmonella spp. to antimicrobials (Smolensk, 1999)

Still, few clinical and environmental strains of S.typhimurium resistant to cefotaxime were isolated in St. Petersburg in 1996. The data from Ekaterinburg show that in 1999 about 17.7% of Salmonella were resistant to ampicillin and ampicillin/sulbactam, 13.8% - to tetracycline, and 6.1% - to trimethoprim/sulfamethoxazole. All tested strains were susceptible to fluoroquinolons. Furthermore a clinical strain resistant to third generation cephalosporins and susceptible to fluoroquinolons and trimethoprim/sulfamethoxazole was isolated in Ekaterinburg.

Mycobacterium tuberculosis

The survey of drug-resistant tuberculosis in north-western Russia (Komi Republic, Pskov, Novgorod, St. Peterburg and Leningrad region, Karelia, Vologda, Arhangelsk, and Murmansk) show that primary resistance to at least one drug incresed from 17% to 24% from 1991-1994. The proportion of secondary resistant mycobacteria did not change significantly and was about 50%.

In Leningrad region primary resistance in 1992-1994 was 29.2%, while the prevalence of primary multidrug resistant strains was 5.1%. The proportion of isolates with secondary resistance to at least one drug did not change significantly with time: 45.6% among extrapulmonary and 69.5% among pulmonary isolates. The prevalence of secondary multidrug resistance among pulmonary isolates increased over time and achieved 33% versus 8.8% among extrapulmonary isolates.

In Ivanovo region primary multidrug resistance of Mycobacteria spp. was 3.8% in 1998. The survey of mycobacterial resistance in Tomsk (1995-1996) proved primary resistance in 27.7% and multidrug resistance in 3.4% isolates.

Nosocomial Pathogens

Staphylococcus aureus and coagulase-negative staphylococci

According to the data, based on the multicentre study of Staphylococcus susceptibility to antibiotics in Moscow and St. Petersburg in 1998, the frequency of methicillin-resistant staphylococci (MRS) ranged from 0 to 40% for S.aureus and from 0 to 65.9% for coagulase-negative staphylococci (CNS). In general methicillin resistance in St. Petersburg (4.1%) was much lower than in Moscow (33.4%). All MRS isolates were susceptible to vancomycin. Susceptibility of S.aureus to fusidic acid, rifampicin and ciprofloxacin was 95%, 84% and 70%, respectively. Corresponding values for CNS isolates were somewhat lower (80%, 85% and 61%, respectively).

Enterococcus spp.

The multicentre trial of Enterococcus antibiotic susceptibility in Moscow and St. Petersburg (1995-1996) revealed that 84% and 85% of E.faecalis isolates were susceptible to ampicillin and ampicillin/sulbactam respectively, the frequency of high-level resistance amounted to 44% for streptomycin and 25% for gentamicin. All strains were susceptible to vancomycin, 75% - to ciprofloxacin. As for E.faecium and rare species of Enterococcus spp. more than 70% of them were resistant to ampicillin and ampicillin/sulbactam, high-level resistance to aminoglycosides exceeded 60%.

The results of the epidemiological study of antibiotic resistance of stool isolates of Enterococcus spp. collected from premature borne children are presented in Table 6.

Table 6. Resistance (%) of Enterococcus spp. to antibiotics (Smolensk)

* Intermediate

Enterobacteriaceae

Antibiotic resistance rates of some nosocomial pathogens obtained in multicentre study NPRS-1997 in Moscow, St. Petersburg, Smolensk, Krasnodar, Kazan, N. Novgorod, Ekaterinburg, Novosibirsk, Krasnoyarsk) are shown in Table 7.

Table 7. Resistance (%) of gram(-) bacteria isolated in ICU in Russia (NPRS-1997)

The resistance to piperacillin varied from 44% in E.coli to 88% in Acinetobacter spp.; to piperacillin/tazobactam - from 11% to 85% in E.coli and Acinetobacter spp. respectively. High rates of resistance to third generation cephalosporins were seen in K.pneumoniae (26-33%), due to the ESBL production, and in Enterobacter spp. (56-60%). Gentamicin resistance values ranged from 13% in E.coli to 91% in Acinetobacter spp. The most active agents were imipenem, ciprofloxacin and amikacin.

According to the data from «Micromax» Project (Table 8) carried out in 8 hospitals in Moscow, Smolensk and Ekaterinburg, the isolates of E.coli and Proteus spp. were highly susceptible to b-lactam antibiotics with no or little variations in different centers. At the same time Klebsiella spp. strains appeared to be less susceptible to third generation cephalosporins (about 40% were resistant to ceftriaxone and 31% to ceftazidime) while only 16% were non-susceptible to cefepime. Imipenem was active against all enterobacteria tested.

Table 8. Resistance (%) of nosocomial gram(-) bacteria to antibiotics («Micromax» Project, 1998)

Pseudomonas aeruginosa

NPRS-1997 showed that about 50% of P.aeruginosa strains were resistant to piperacillin, 41% - to piperacillin/tazobactam, and over 10% to ceftazidime. Imipenem-resistant strains were comparatively rare in all centers (0-11%). The frequency of resistance to gentamicin was 75%, to amikacin - 7%, and to ciprofloxacin - from 6 to 42%.

The results of multicentre study in Moscow showed high rates of P.aeruginosa resistance to antipseudomonade b-lactams: 45% to piperacillin/tazobactam, 55% to ceftazidime, and 47% to cefepime. The most active antibiotics were imipenem (18% resistant strains) and meropenem (19% resistant strains). The resistance to ciprofloxacin was also quite high (45%), and aminoglycoside resistance varied from 11% for amikacin to over 60% for gentamicin.