Introduction

In recent years, the prevalence of multidrug-resistant bacteria represented by gram-negative bacilli has rapidly increased, which have posed great challenges for the clinical anti-infective treatment. Bacterial resistance surveillance is one of the most important basic tasks to understand the change of resistant bacteria and to prevent its further spreading. In this analysis, we reported the antimicrobial resistance of clinically important pathogens from China antimicrobial surveillance network (CHINET).

Materials and methods

Participating hospitals and bacterial strains

A total of 44 hospitals were obtained in the CHINET in 2018. Most of the hospitals included are the largest in each province or city; altogether, they represent 26 provinces or cities (about nine hundred million population). In order to avoid duplicate counts, only one isolate from the same species was included per patient, based on the personal identifying code and hospital, per year. Species identification of the isolates was performed by automated systems such as Vitek, Phoenix, or MALDI-TOF.

Antimicrobial susceptibility testing

Antimicrobial susceptibility testing was performed followed the guidelines recommended by the Clinical and Laboratory Standards Institute (CLSI) [1], in which the US FDA standard was adopted for tigecycline test, and the criteria for polymyxinB against Enterobacteriaceae are referred to the epidemiological cutoff value of colistin in the CLSI file (MIC ≤ 2 μg/mL for wild strains; MIC ≥ 4 μg/mL for non-wild strains).

Quality control

Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were used as internal quality control. Carbapenem-resistant Enterobacteriaceae (CRE) is defined as being resistant to any of imipenem, meropenem, or ertapenem.

Results

Percentage of major clinical strains

A total of 244,843 clinical isolates were collected, of which 69,057 strains of gram-positive bacteria accounted for 28.2% and 175,786 strains of gram-negative bacteria accounted for 71.8%. Most isolates (39.7% of 244,843) were cultured from lower respiratory tract. Of those, the five major species were most often isolated (65.5%). Urine isolates were mainly from women (66.7% of five major species) and E. coli was mostly often isolated (46.6%). From blood, the most frequently organism was also E. coli (23.1%). The five major species accounted for 30.3% in cerebrospinal fluid. The percentage of five major species isolated from four specimens is shown in Table 1.

Table 1 Percentage of five major species isolated from four specimens
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Susceptibility of gram-positive cocci to antimicrobial agents

For MRSA, the resistance rate to most antimicrobial agents was significantly higher than that of MSSA strains. However, the resistance rate of MRSA to trimethoprim-sulfamethoxazole was lower than that of MSSA except for in urine specimens (20.5% and 15.5%). 79.6% of MRSA is sensitive to trimethoprim-sulfamethoxazole, and 98.3% of MSSA is sensitive to rifampicin. The resistance rate of MRSA isolated from cerebrospinal fluid to gentamicin, rifampin, and levofloxacin is higher than other three specimens. Four strains of S. aureus isolated from blood are resistant to linezolid. No vancomycin-resistant strain was found in Staphylococcus (Table 2).

Table 2 Resistance rates of Staphylococcus spp. to antimicrobial agents (%)
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Susceptibility and resistance rate of gram-negative bacilli to antimicrobial agents

From four specimens, the resistance rate of E. coli to ceftazidime, cefepime were close to or higher than 30%. The resistance rate of E. coli to ciprofloxacin and trimethoprim-sulfamethoxazole were nearly 70%. The resistance rates of E. coli to β-lactam/β-lactamase inhibitor combinations and carbapenems were still low, but the resistance rate of Klebsiella pneumoniae to imipenem and meropenem was fluctuated around 18.6% and 64.1%, especially the cerebrospinal fluid isolates. The resistance rate of Klebsiella pneumoniae to other agents was higher than that of E. coli besides ciprofloxacin and trimethoprim-sulfamethoxazole, to polymyxin B and tigecycline were lower (0 and 5.6%) (Table 3). The resistance rates of Klebsiella pneumoniae to imipenem and meropenem was increased to 25% and 26.3% in 2018 respectively from 3.0% and 2.9% in 2005, and the resistance rate increased was more than 8 times (Fig. 1).

Table 3 Resistance rates of Enterobacteriaceae to antimicrobial agents(%)
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Fig. 1
figure 1

Resistance Change of Klebsiella pneumoniae to Imipenem and Meropenem between 2005 and 2018

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The resistance rate of 18,534 strains of Pseudomonas aeruginosa to imipenem and meropenem was fluctuated around 17.1% and 57.4% respectively. especially for cerebrospinal fluid isolates, the resistance rate of P. aeruginosa to amikacin was less than 10% respectively, meantime the resistance rate of P. aeruginosa to other agents was < 30%. The resistance rate of P. aeruginosa to imipenem and meropenem showed a steady downward trend from 2005 to 2018 (Fig. 2). The resistance rate of A. baumannii to the agents was higher than that of P. aeruginosa. From urine, the resistance rate of A. baumannii to the agents was fluctuated around 21.8% and 46.7% respectively (Table 4). The resistance rate of cerebrospinal fluid isolates was higher than other three specimens. The resistance rate of A. baumannii to imipenem and meropenem showed a rapid rising trend from 2005 to 2018 (Fig. 3).

Fig. 2
figure 2

Resistance Change of Pseudomonas aeruginosa to Imipenem and Meropenem between 2005 and 2018

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Table 4 Resistance rates of non-fermentative gram-negative bacilli to antimicrobial agents (%)
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Fig. 3
figure 3

Resistance Change of Acinetobacter baumannii to Imipenem and Meropenem between 2005 and 2018

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Discussion

Results of 2018 CHINET antimicrobial surveillance network: (1) The total number of strains collected in 2018 was 244,843, an increase of 28.5% compared with 190,610 in 2017 [2]. Except for E. coli, the prevalence of most bacteria out of Enterobacteriaceae was slightly higher than that in 2017, among of which, Klebsiella spp. was the most. The prevalence of Acinetobacter spp. in non-fermented gram-negative bacilli was increased slightly, but P. aeruginosa remained unchanged. (2) Routine susceptibility testing results show that either Enterobacteriaceae or A. baumannii, tigecycline susceptibility testing is of false mediation or false drug resistance, the laboratory should promptly use other methods for review and confirmation.

The bacterial resistance of gram-negative bacteria is becoming more and more serious, and the treatment of certain drug-resistant infections is extremely limited in clinical practice [3,4,5]. Carbapenems have been considered as the last line of defense against gram-negative infections in the past 10 years. With the rapid increase in the prevalence of carbapenem-resistant strains, especially K. pneumoniae, P. aeruginosa, and A. baumannii, clinical anti-infective treatment has become a difficult problem. CHINET surveillance data [2, 3, 6] over the years showed that the resistance rate of K. pneumoniae to imipenem and meropenem was respectively increased from 3.0% and 2.9% in 2005 to 25% and 26.3% in 2018, with more than 8-fold increase. Besides, the annual isolation rate of K. pneumoniae was also steadily increasing. The surveillance results showed that the resistance rate of K. pneumoniae to carbapenems was > 20%; the resistance rate of Klebsiella pneumoniae isolated from only 1 hospital out of 5 children’s hospitals to imipenem was 2.5%, while the resistance rate of Klebsiella pneumoniae isolated from the remaining hospitals was ranged from 32.1 to 45.5%. Nevertheless, the resistance rates of P. aeruginosa and A. baumannii to imipenem were close to 30.7% and 73.2% respectively. Among 13,102 strains of CRE, the top three isolates were K. pneumoniae (73.5%, 9625/13102), E. coli (8.6%, 1123/13102) and Enterobacter cloacae (5.4%, 701/13102). The resistance rate of Klebsiella spp. isolated from 44 hospitals to imipenem was in range of 0% to 53.1%, and the resistance rate of P. aeruginosa to imipenem was in range of 1.7 to 45.2% to imipenem; the resistance rate of Acinetobacter spp. to imipenem was from 3.8 to 91.4%. Studies have shown that carbapenem-resistant strains are highly resistant to most commonly used antimicrobial agents; the majority of resistant strains are only sensitive to tigecycline and polymyxin B. In order to cope with infections caused by such super-resistant bacteria, the laboratory person shall actively communicate with clinical to add some potentially effective drug tests, such as polymyxinB, tigecycline, and ceftazidime-avibactam. However, microbiological laboratory personnel should pay special attention to problems in running susceptibility testing for polymyxin and tigecycline. Currently, CLSI does not recommend to use disk diffusion method, agar dilution method, or other drug susceptibility methods for polymyxinB antimicrobial susceptibility testing, which must use the microbroth dilution method. In vitro activity of tigecycline are affected by many factors, including the media type, preparation time, detection method of medium, type of strain, selection of breakpoint, etc. [7]. Therefore, when tigecycline susceptibility was measured by laboratory paper dispersion method and automated systems method, the susceptibility should be further confirmed using microbroth dilution method if moderately sensitive or resistant results were shown.

Producing KPC-type carbapenemase or NDM-1 metalloenzyme is the most important resistance mechanism of Enterobacteriaceae to carbapenems, and the resistance mechanisms of different populations and strains from different regions showed some difference. The results have showed that the CRE strains isolated from child patients mainly produced NDM-1 type metalloenzyme, while the strains isolated from adult patients mainly produced KPC-type carbapenemase. From the perspective of the geographical distribution, the clinically isolated CRE strains in northern China hospitals produced more NDM-1 metalloenzyme strains and less KPC-type carbapenemase strains than that in the Southern China hospital [8]. In addition, clinical laboratories shall strengthen the detection of class D carbapenemases in CRE strains, in particular, the OXA-48 carbapenemase family including OXA-181 and OXA-232 carbapenemases. Since the current methods recommended by CLSI and related literature are unable to effectively detect OXA-type carbapenemase, it may appear as a false-negative result. Studies have shown that in China, there are reports about the prevalence of clonal strains induced by the infection of K. pneumonia producing OXA-type carbapenemase. These drug-resistant strains were mainly measured in the strains isolated from children patients [9]. In the future, the implementation of a multicenter epidemiological investigation on CRE strains is required in our country, so as to clarify the prevalence of CRE strains among the inpatients, in particular in those with critical illness. It could provide an important reference for effective infection prevention and control subsequently.