Introduction: The prevalence of Klebsiella pneumoniae has rapidly increased in recent years and the distribution differed greatly by region, We aimed to study the relationship between antibiotic resistance and K. pneumoniae , especially carbapenem-resistant Klebsiella pneumoniae (CRKP) in our tertiary hospitals from 2014 to 2018. Methodology: The antibiotic consumption data of K. pneumoniae were expressed as the defined daily dose (DDD) per 100 inpatient days (DDDs). K. pneumoniae which isolated from clinical samples in hospital between January 2014 and December 2018 were retrospectively analyzed, and the correlation between antibiotic resistance rate and antibiotic frequency was analyzed. Results: From 2014 to 2018, a total of 2295 strains of K. pneumoniae were isolated, with the detection rates of 8.2%, 9.2%, 11.9%, 13.4% and 14.0%. There were 423 strains of CRKP, with the detection rates of 7.5%, 5.8%, 17 . 8% 24.2% and 25.2% respectively. K. pneumoniae showed di fferent degrees of resistance to antibiotics and showed an increasing trend year by year to carbapenems. The resistance rate of imipenem was 2.5% , 2.8% , 9.9% , 12.3% , 13.4%, and the resistance rate of meropenem was 2.0% , 3.0% , 8.8% , 12.6% , 12.7%, respectively. The resistance rate of most other drugs decreased. The DDDs values of cefoperazone/sulbactam, piperacillin-tazobactam and gentamicin showed a strong positive correlation with K. pneumoniae drug resistance rate (r > 0.8, P < 0.05) . Conclusions: The detection rate of K. pneumoniae and CRKP increased year by year, which was closely related to the dose of antibiotics. Strengthening the management of antimicrobial drugs and standardising the use of antimicrobial prescriptions were of great significance for delaying the emergence of drug-resistant bacteria.
Klebsiella pneumoniae is a gram-negative bacillus, which is an essential condition pathogenic bacterium and iatrogenic infectious bacterium in Enterobacteriaceae Klebsiella. In recent years, the bacterial resistance rate has been increasing with the widespread use of antibacterial drugs and the rapid change of bacteria, especially carbapenem-resistant K. pneumoniae (CRKP), CHINET data showed that the detection rate of CRKP was 13.8% in 2007 [
Klebsiella pneumoniae were isolated from various patient bodily fluids/sites including sputum, urine, pus, blood, sterile body fluid, surgical wound, submitted by the clinical department of the hospital from 2014 to 2018. The samples to exclude the same patient during a hospital and the same strain of the same part were separated and identified by Vitek-2 system (French bio-Merieux company) and the K-B method following guidelines recommended by the Clinical and Laboratory Standards Institute (CLSI), 2011 (M100-S21) [
The modified Hodge test (MHT) was used to dilute the suspension of K. pneumoniae ATCC 700603 0.5 M. turbidity bacteria with sterile normal saline at 1:10 and evenly spread on the MH plate. After drying at room temperature for 3 - 10 min, meropenem was pasted in the middle, and the bacteria to be tested were streaked from the edge of the paper sheet to the edge of the plate. The results were observed after 18 - 24 h incubation at 35 C. Result: when the MIC of meropenem ≥ 2 ug/ml, it was a carbapenem-resistant strain.
The antibacterial drug data was derived from the hospital HIS systems from January 2014 to December 2018. The antibacterial drug distribution information of the inpatient pharmacy and the relevant information in Excel. The total consumption is calculated and using the defined daily dose (DDD) classification recommended by the World Health Organization (WHO) (http://www.whocc.no/atc_ddd_index/). Inpatient days were calculated by multiplying the quarterly total number of hospital discharges with the mean number of days of hospitalization [
The trend over time for antimicrobial consumption and rates of KP was calculated independently by Pearson’s correlation analysis. The Pearson’s correlation coefficient (r) between the bacterial resistance rate and the DDDs value of antibacterial drugs was calculated: r > 0.8, which was considered to have a strong correlation between them; r < 0.3, the relationship between them is considered to be weak; P < 0.05 is considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics 24.0.
From 2014 to 2018, a total of 2295 strains of K. pneumoniae were detected, and the detection rate increased from 8.3% in 2014 to 14.1% in 2018, showing an increasing trend year by year. Among them, 423 CRKP strains were detected, and the isolation rate was from 7.3% in 2014, 5.8% in 2015 to 25.2% in 2018. The specific data are shown in
A total of 2295 K. pneumoniae were isolated from sputum, urine and pus, and their composition ratios were 67.2%, 12.3% and 7.8%, respectively. But CRKP was mainly derived from sputum, blood and urine, with a composition ratio of 50.4%, 13.9% and 12.8%, respectively. The specific data are shown in
K. pneumoniae have different degrees of resistance to antibacterial drugs, and the resistance to carbapenems has been a significant increasing trend. From 2014 to 2018, The resistance rates of imipenem are 2.53%, 2.80%, 9.90%, 12.30% and 13.41%, the drug resistance rates of meropenem were 2.04%, 3.00%, 8.80%, 12.60%, and 12.72%, respectively. The drugs with the highest DDDs value were cefoperazone/sulbactam and showed an upward trend each year. The smaller values were ciprofloxacin and imipenem. The correlation between the resistance rate of KP to common antibacterial drugs and the changes in the corresponding antibacterial drugs DDDs value from 2014 to 2018 is shown in
| Year | n/Strain | KP | CRKP | ||
|---|---|---|---|---|---|
| Strain | Rate (%) | Strain | Rate (%) | ||
| 2014 | 3572 | 292 | 8.2 | 22 | 7.4 |
| 2015 | 3561 | 329 | 9.2 | 19 | 5.8 |
| 2016 | 3866 | 461 | 11.9 | 82 | 17.8 |
| 2017 | 4156 | 556 | 13.4 | 135 | 24.3 |
| 2018 | 4662 | 650 | 14 | 165 | 25.2 |
| Total | 19,817 | 2288 | 11.5 | 423 | 18.5 |
| Strain source | KP | CRKP | ||
|---|---|---|---|---|
| Strain (n = 2295) | Rate (%) | Strain (n = 423) | Rate (%) | |
| sputum | 1542 | 67.2 | 213 | 50.4 |
| urine | 283 | 12.3 | 54 | 12.8 |
| pus | 179 | 7.8 | 40 | 9.5 |
| sterile body fluid | 125 | 5.4 | 29 | 6.9 |
| blood | 103 | 4.5 | 59 | 13.9 |
| surgical wound | 63 | 2.7 | 28 | 6.4 |
| Antibacterial drugs | Drug resistance rate of KP (%) | DDDs | r | P | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2014 | 2015 | 2016 | 2017 | 2018 | 2014 | 2015 | 2016 | 2017 | 2018 | ||||
| Amikacin | 20.5 | 18.5 | 14.4 | 13 | 13.1 | 248 | 253 | 336.2 | 416.4 | 452.6 | −0.932 | 0.021 | |
| Ampicillin | 100 | 99.6 | 100 | 99.8 | 99.7 | - | - | - | - | - | - | - | |
| Ciprofloxacin | 23.8 | 23.5 | 26.5 | 30.5 | 30.4 | 185.5 | 172.4 | 147.2 | 132.8 | 165.8 | −0.682 | 0.205 | |
| Ceftriaxone | 56.6 | 54.6 | 62.9 | 47.2 | 46.3 | 6831 | 7184 | 9374 | 14634 | 15494 | −0.772 | 0.126 | |
| Cefoperazone/sulbactam | 10.8 | 9.8 | 13.9 | 20.5 | 22.3 | 25,642 | 27,283 | 36,402.7 | 41,241.4 | 46,848.6 | 0.964 | 0.008 | |
| Cefuroxime | 62.5 | 59.5 | 73.4 | 49.2 | 48 | 465.3 | 495.7 | 2221 | 5105.7 | 5865.5 | −0.697 | 0.191 | |
| Cefazolin | 65.6 | 62.6 | 54.4 | 54.3 | 58.5 | 5869.2 | 5511.7 | 4627.3 | 9294 | 10,684 | −0.277 | 0.651 | |
| Cefepime | 39.5 | 39.4 | 29.7 | 26.1 | 25.6 | - | - | - | 182.4 | - | - | - | |
| Cefoxitin | 31.6 | 29.6 | 35.9 | 22.1 | 23.1 | - | - | - | - | - | - | - | |
| Gentamicin | 43.4 | 42.4 | 30.4 | 22.6 | 21.9 | 4754.8 | 4563.3 | 3024.3 | 2989.7 | 2579.6 | 0.967 | 0.007 | |
| Imipenem | 2.5 | 2.8 | 9.9 | 12.3 | 13.4 | 123.8 | 132.5 | 389.3 | 306.8 | 314.4 | 0.873 | 0.053 | |
| Levofloxacin | 25.2 | 22.2 | 23.9 | 26 | 25.9 | 15,483.7 | 16,539.8 | 21,092.4 | 20,170.4 | 25,367.5 | 0.48 | 0.413 | |
| Meropenem | 2 | 3 | 8.8 | 12.6 | 12.7 | 6537.9 | 4970.8 | 6750.7 | 10,914.4 | 12,835.8 | 0.876 | 0.052 | |
| Piperacillin/tazobactam | 9.4 | 10.4 | 13.2 | 17.1 | 17.2 | 2146.6 | 2395.6 | 5356.2 | 6733.5 | 7483.4 | 0.98 | 0.003 | |
| Fuxin Xinming | 46.5 | 48.5 | 42.7 | 28.1 | 27.6 | - | - | - | - | - | - | - | |
Note: - indicates that this item has no data.
The strength of association between DDDs of cefoperazone/sulbactam, piperacillin/tazobactam, gentamicin and resistance rate of K. pneumoniae were very high (r = 0.964, 0.980, 0.967), and that the correlation coefficient is very highly significantly different from zero (P < 0.01). The values of DDDs of amikacin and ciprofloxacin were negatively correlated with the resistance rate of K. pneumoniae (r = −0.965, −0.972, P < 0.05). The DDDs of levofloxacin had a correlation with the K. pneumoniae resistance rate of 0.8 > r > 0.6, P < 0.01. The DDDs of meropenem had a strong positive correlation with K. pneumoniae resistance rate r > 0.8, but P > 0.05 showed no difference. Imipenem 0.5 < r < 0.8, P > 0.05, its correlation is not large. For other antibacterial drugs, r < 0.8, P > 0.05, the correlation is not great.
Our study highlights the rising resistance rates of K. pneumoniae which isolated our hospital from 2014 to 2018, especially the resistance rates of CRKP has rapidly increased from 7.5% in 2014, 5.8% in 2015 and 17.8% in 2016, 24.2% in 2017 to 25.2% in 2018. In our study our hospital should pay attention to the resistance of CRKP because carbapenems are the last line in defence against the pathogen, clinical drug treatment is facing severe challenges and changes, and it is a wake-up call for clinicians and pharmacists. This article wants to provide valid data for the clinic by counting the correlation between the drug resistance rate of bacteria and the frequency of use of antibacterial drugs DDDs. Reasonable norms, to eliminate the phenomenon of unindicated medication and medication for too long [
Antimicrobial resistance (AMR) is currently one of the most urgent public health issues in the world [
From the data, it was found that 15 antibacterial drugs of K. pneumoniae were tested for in vitro susceptibility. The increase in drug resistance rate was directly related to the amount of clinical use. The DDDs of cefoperazone/sulbactam rose from 27,283.0 to 41,241.4. The resistance rate of cefoperazone/sulbactam to K. pneumoniae increased from 9.8% to 20.5%, and the DDDs of piperacillin sodium/tazobactam sodium increased from 2395.6 to 6733.5 and K. pneumoniae to cefoperazone/sulbactam The rate increased from 10.43% to 17.09%, and the DDDs of gentamicin decreased from 4563.3 to 2989.7, which was highly correlated with the resistance rate of K. pneumoniae to gentamicin from 42.4% to 22.6% (r = 0.953, 0.938, 0.928, P < 0.05); the values of DDDs of amikacin and ciprofloxacin were strongly negatively correlated with the resistance rate of K. pneumoniae (r = −0.965, −0.972, P < 0.05). The meropenem DDDs values were not significantly correlated with K. pneumoniae drug resistance rate (r > 0.8, P > 0.05). Imipenem 0.5 < r < 0.8, P > 0.05, its correlation is not large. It is suggested that the emergence of bacterial resistance is not only related to antibacterial drugs DDDs but may also be related to factors such as cross-resistance of bacteria. Among them, the widespread use of broad-spectrum β-lactamase inhibitors affects the effect of carbapenem drugs on the Antibacterial activity of K. pneumoniae. Zhan [
In the study, the monitoring data shows that the resistance of K. pneumoniae to carbapenem antibacterial drugs is on the rise because carbapenem antibacterial drugs are the most effective antibacterial drugs for the treatment of K. pneumoniae infections [
After 5-year period analysis of drug resistance rates, although K. pneumoniae has aminoglycosides (amikacin), enzyme-inhibitors (piperacillin/tazobactam, cefoperazone/sulbactam), The sensitivity of cephalosporins (cefoxitin) and carbapenems (imipenem, meropenem) has remained at a high level, and the resistance rate of the third and fourth generation cephalosporins has increased, especially CRKP is gradually increasing. Therefore, the drug resistance rate of K. pneumoniae is highly correlated with the use of various antibacterial drugs. Rotation of antibacterial drugs can reduce the drug resistance rate of bacteria.
Our data demonstrate a significant increase in the prevalence of K. pneumoniae and the consumption of enzyme-inhibitors in our hospital. We found that the high incidence of CRKP is associated with increased enzyme-inhibitors usage in our hospital. Future work is needed to elucidate the factors which influence the increased consumption of enzyme-inhibitors usage in our hospital.
This work was funded by the Chengde Science and Technology Planning Project (No. 201701A094).
The authors declare no conflicts of interest regarding the publication of this paper.
Hu, J.L., Xiao, X., Hu, C.C., Wang, R., Zhao, Y.W. and Zhu, X.Q. (2020) Correlation between a Change of Drug Resistance of Klebsiella pneumoniae and Defined Daily Doses of Antimicrobial Agents from 2014 to 2018. Pharmacology & Pharmacy, 11, 299-305. https://doi.org/10.4236/pp.2020.1111024