Multidrug-resistant organisms in intensive care units and logistic analysis of risk factors

lNTRODUCTlON

Intensive care unit(ICU)patients are critically ill and have low immunity.They undergo various traumatic medical procedures during diagnosis and treatment.The use of high-dose hormones and broad-spectrum antibiotics increase the incidence of nosocomial infection in ICU patients.Therefore,it is necessary to explore the causes of nosocomial infection in the ICU and provide a basis for the prevention and control of nosocomial infection in the ICU.This study described multidrug-resistant bacterial infection in ICU patients from January 2016 to December 2019,and analyzed the risk factors for infection by multidrug-resistant bacteria in ICU patients.

MATERlALS AND METHODS

Research methods

Bacteria were isolated from collected samples for identification and analysis following the National Operating Rules for Clinical Examination(third edition).BD PhoenixTM100 automatic bacterial identification and analysis instrument was used for cell identification.Drug sensitivity test was carried out by paper disk(provided by Oxoid)Agar diffusion method(Kirby-Bauer method).()ATCC27853,()ATCC25923 and()ATCC25922 were used as quality control strains.

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Inclusion and exclusion criteria

Inclusion criteria were:(1)According to the definition of diagnostic criteria for nosocomial infection(2001)issued by the Ministry of Health of the People’s Republic of China,and the etiological diagnosis was multidrug-resistant bacterial infection;and(2)Inpatients in the ICU.

Drug resistance trend analysis and prevention and control of main pathogens in tertiary hospitals of Hebei Provincial Department of health,No.20210845;and Analysis of drug and drug resistance trend and prevention and control of pathogens in major general hospitals of Baoding science and technology support plan project,No.17zf79.

Exclusion criteria were:(1)Diagnosis did not meet the diagnostic criteria for nosocomial infection issued by the Ministry of Health of the People’s Republic of China;(2)Diagnosis of multidrug-resistant bacterial colonization without clinical infection symptoms;(3)Contaminated samples of multidrugresistant bacteria;and(4)Natural resistant strains.

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Statistical analysis

Pathogenic bacteria detected in nosocomial samples were analyzed and sorted out by real-time monitoring system for nosocomial infection control in Xinglin.Retrospective analysis was used to investigate and collect patient records and test data.Data analysis was performed using SPSS 22.0.Logistic regression analysis was used to perform univariate and multivariate analyses for independent risk factors for multidrug-resistant infection.

RESULTS

Sample collection

A total of 2070 cases of ICU infection were recorded.The causative pathogens were mainly collected from sputum in 1139 cases(55.02%),blood in 521(25.17%),and drainage in 117(5.65%)(Table 1).

Distribution of pathogenic bacteria

Among the 1051 strains of main pathogens identified in ICU,966 were Gram-negative bacteria,accounting for 91.91% of the total number of pathogens.()was most common strain,accounting for 35.97%(378/1051)of the total strains,followed by(24.74%),(21.79%)and()(9.42%).was the most common Grampositive bacteria strain with 8.09%(85/1051)(Table 2).

Drug-resistance trends and analysis of main pathogens

:Resistance rates ofto minocycline in 2017 and 2019 were 28.41% and 32.42%,respectively.Resistance rates of this strain to other antimicrobials were ＞ 40%(Table 3).Energy allocation rate to the antimicrobial drug meropenem was 74.6%,and imipenem resistance rate was 75.66%(Table 4).

:Carbapenem,piperacillin/tazobactam,amikacin,and cefoperazone/sulbactam showed inhibitory activity against.Analysis of 2019 data showed 21.4%(5/22)rate of resistance against cefotaxime and 13.6%(3/22)against tobramycin(Table 4).Resistance rate ofagainst meroxifen was 14.41%(33/229),whereas resistance rate against imipenem was 15.28%(35/229)(Table 3).

The authors will thank for Yan JP great help.

I think he is not in his right senses! said the Princess, and walked on, butwhen she had gone a little way, she stopped again. One must encourage art, said she, I am the Emperor s daughter. Tell him he shall, as on yesterday,have ten kisses from me, and may take the rest from the ladies of the court.

:Analysis of 2019 data showed thatwas 12.5% resistant to cefoperazone/sulbactam(3/27)and generally insensitive to other antibiotics.Drug resistance againstin 2019 was severe compared with previous years(Table 4).Resistance rate ofto Meropenem in the previous 4 years was 20.20%(20/99),whereas resistance rate ofto imipenem was 19.9%(19/99)(Table 3).

:Incidence of methicillin resistance ofat the time of the study was 64.71%(55/85).In the previous 4 years,no resistance was recorded for linezolid and vancomycin antibiotics against(Table 3).

Logistic regression analysis

A ratio of 1:1 was used to analyze risk factors for multidrug-resistant bacterial infection in 208 patients hospitalized in ICU with nosocomial infection.In addition,208 patients hospitalized at the same time,and with comparable age,sex and symptoms were selected as a control group.Factors with≤ 0.05 were included in the logistic regression model to avoid the influence of confounding factors.Logistic regression analysis showed that mechanical ventilation and urine tube intubation were risk factors for infection with multidrug-resistant bacteria(Tables 5 and 6).

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DlSCUSSlON

ICU patients are in critical condition,and are often accompanied with multiple organ dysfunction and severe immune dysfunction.Ventilator and invasive operation may result in damage to physiological barriers of patients,and risk of infection in ICU patients is higher compared with patients in other departments[1].ICU patients use antibiotics at a higher frequency,higher dose and longer duration,andinfection with multiple drug-resistant bacteria(multidrug-resistant organisms;MDROs)is severe compared with patients in other departments.Surveillance results of the European Centers for Disease Control and Prevention show that drug resistance of common pathogenic bacteria such asincreased from 1997 to 2018[2].Therefore,studies on nosocomial infections should be carried out.Intervention with drugs that are effective against drug-resistant pathogenic bacteria can reduce the incidence of MDROs.This study explored distribution of pathogens implicated in nosocomial infections in ICU and degree of drug resistance to a variety of antibiotics.The findings of this study will guide on rational use of drugs in clinics,to reduce the occurrence of drug-resistant bacteria.Furthermore,this study provides an effective scientific basis for improving clinical efficacy of antibiotics.

For a while they just hung there to each other laughing and crying and saying things without meaning. She d say a few words like, It was the bus station I meant and he d kiss her speechless and tell her the many things he had done to find her. What apparently13 had happeded three years before was that May had come by bus, not by train, and in her telegram she meant bus station, not railroad station. She had waited at the bus station for days and had spent all her money trying to find Harry. Finally she got a job typing.，，，。“——”，。，3。“”“”。，。，。

Antibiotics with a resistance rate ＞ 40% to major pathogenic bacteria should be used cautiously.Antibiotics with a resistance rate ＞ 50% to major pathogenic bacteria must be selected and used based on drug sensitivity test results.Use of antibiotics must be stopped if the drug resistance rate of the main pathogenic bacteria is ＞ 75%.Feedback results of bacterial resistance must be investigated and analyzed,to determine whether clinical use of the drug can be continued.Therefore,it is important to explore detection and analysis of drug resistance of pathogenic bacteria in hospitals[3].is a common cause of opportunistic infection in humans[4].Drug-resistance and isolation rates of this strain have gradually increased in recent years with higher rates compared with the incidence of

infections.was the main pathogen causing ICU colonization and nosocomial infection.Several studies have reported thatis the most sensitive strain to imipenem.In addition,is highly sensitive to combination therapies of β-lactam and enzyme inhibitors such as cefoperazone/sulbactam and ampicillin/sulbactam.Sulbactam,an enzyme inhibitor,has direct antibacterial properties and an inhibitory effect against β-lactamases.Therefore,sulbactam is used in combination with cefoperazone and ampicillin.This strain is resistant to most antimicrobial agents and can be cloned and spread rapidly among strains.Surveillance data of drug resistance of CHINET bacteria in China in 2018 showed that resistance rates of imipenem and meropenem against this strain were 73.2% and 73.9%,respectively.In addition,resistance rates to cefoperazone/sulbactam and minocycline were 49.7% and 38.8% respectively.Resistance rates to polymyxin B and tigecycline were low(0.7% and 5.0%),whereas resistance rates to other tested drugs were ＞ 40%.Resistance rate ofto imipenem and meropenem significantly increased between 2005 and 2018.Resistance rates of 378 strains ofisolated from ICU between 2016 and 2019 to imipenem and meroxifen were 75.66% and 74.6%,respectively.Resistance rates to cefoperazone/sulbactam during the 4 years were 61.27%,60.71%,48.81% and 68.4%,respectively.Further,resistance rates to quinolones in the 4 years were 83.10%,73.86%,80.95% and 81.36%,respectively.These rates were higher compared with rates recorded in data released in 2016 on sensitivity of bacteria to antimicrobial agents in CHINET in China.In addition,the report showed that rates of resistance to minocycline in 2017 and 2019 were 28.41% and 32.42% respectively.Notably,＞ 40% resistance rates to other antibiotics were recorded.These findings indicate that hospitals should monitor resistance ofto a variety of antimicrobial agents in real time.Furthermore,mechanisms of antimicrobial resistance should be explored,accurate clinical use of antibiotics should be ensured,and infection control measures should be improved.These measures will prevent increases in multidrug resistance ofto a variety of antibiotics thus reducing occurrence of multidrug-resistant strains[5].

Logistic analysis results showed that mechanical ventilation and urinary tube intubation were risk factors for infections caused by multidrug-resistant bacteria.This finding implies that our medical staff should carefully consider the necessity before performing the above procedures,to reduce infections caused by multidrug-resistant bacteria.Mechanical ventilation,urinary catheterization and other invasive procedures increase point of entry for pathogens thus increasing resistance level of multi-drugresistant bacteria.Therefore,the important task of preventing and controlling MDRO infection in ICU is to improve the prevention and control measures as soon as possible in the face of the increasing rate of multidrug-resistant infection in the world.

was sensitive to a variety of antibiotics in 2016,2018 and 2019.Energy allocation rates of imipenem and Meropenem resistance in the 4 years were 26.5% and 20.38%,respectively.This finding is important for clinicians when choosing antibiotics.Antibiotics with high sensitivity and low price should be selected based on characteristics and drug sensitivity of common infection pathogens in the ICU,to improve therapeutic effect and reduce economic burden of treatment to patients.

Although bacteria have their own drug-resistance mechanism,the primary reason for high incidence of multidrug-resistant bacteria infection in ICUs is inappropriate use of antibiotics,especially abuse of third-generation cephalosporins[14-17].Studies have reported that nosocomial infection in ICU patients is a major source of mortality.Adoption of clear evidence-based prevention and control methods to significantly reduce incidence of nosocomial infection is an important measure to improve treatment efficacy and prognosis of ICU patients.However,advocacy should be carried out to control nosocomial infection and reduce the rate of antibiotic resistance.The purpose of this study was to explore and analyze the main pathogens of ICU nosocomial infections and their drug resistance[18].The study reports on main pathogenic bacteria of nosocomial infection and corresponding mechanism of drug resistance in the ICU at a specific time,and analyzed drug resistance of pathogenic bacteria after use of antibiotics in the same period.These findings provide a theoretical basis for hospital control of drugresistant infections,so as to improve efficacy of antibiotics and safety of diagnosis and treatment of patients,rational use of antibiotics,and reduce pressure on patients,family members and the wider economy.

is an important pathogen of nosocomial and community infection.The detection rate of multidrug-resistantin a general hospital was approximately 65.82%[11].No strains resistant to linezolid and vancomycin were detected among the strains isolated for the 4 years.Linezolid and vancomycin can be used to treat severe infection caused by Gram-positive cocci.However,widespread use of these antimicrobials will aggravate drug toxicity.These drugs can be used to preventresistance against vancomycin.Further studies should explore measures to control drug resistance against vancomycin[12].Clinical management on use of antibiotics should be carried out,and vancomycin should not be used as the first choice for prevention and routine treatment of staphylococcal bacterial infections.

Logistic regression analysis showed that mechanical ventilation and urinary tube intubation were risk factors for infections caused by multidrug-resistant bacteria.This implies that medical staff should carefully consider the necessity before performing the above procedures.,to reduce infections caused by multidrug-resistant bacteria.Mechanical ventilation,urinary catheterization and other invasive procedures increase point of entry for pathogens,thus increasing resistance level of multidrug-resistant bacteria.Therefore,the important task of preventing and controlling MDRO infection in the ICU is to improve the prevention and control measures as soon as possible,in the face of the increasing rate of multidrug-resistant infection worldwide[13].

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Han Y and Zhang J made equal contributions to the work;Han Y,Zhang J and Zhang HZ

CONCLUSlON

is commonly resistant against extended-spectrum β-lactamase and cephalosporin.Carbapenem antibiotics are some of the most effective for treatment ofinfection.In recent years,carbapenem-resistanthas been widely spread around the world,resulting in a high resistance rate to almost all β-lactam antibiotics and increase in mortality.In 2013,the US Center for Disease Control and Prevention published threat of antibiotic resistance,including carbapenemresistant Enterobacteriaceae as one of the three bacteria in the urgent threat category.In addition,in the 4 years,resistance rates ofto imipenem and meropenem were 19.9% and 20.20%,respectively.The CHINET surveillance report shows that resistance rates ofto meropenem and imipenem in 2013 were 13.5% and 10%,respectively.On the contrary,Enterobacteriaceae are highly sensitive to carbapenem antibiotics,however,drug resistance rate is gradually increasing.Previous studies have reported that infection with carbapenem-resistantcauses a high number of in-hospital deaths[8,9].Case fatality rate ofinfections,which is sensitive to carbapenem,is 25.7%.The case fatality rate of patients infected with carbapenem-resistantis 50%,which is significantly higher compared with that of carbapenem-sensitive.Long-term use of central venous intubation is an independent factor for infections caused by carbapenem-resistant[10].Restrictions on clinical use of broad-spectrum cephalosporins can effectively reduce resistance rate ofto cephalosporins.Therefore,studies should explore characteristics of nosocomial infection of,analyze characteristics of antibiotic resistance,and implement rational distribution of antibiotics,to avoid further evolution of drug-resistant strains.

ARTlCLE HlGHLlGHTS

Research background

There intensive care unit(ICU)patients are critically ill and have low immunity.They will undergo various trauma medical procedures during diagnosis and treatment.The use of high-dose hormones and broad-spectrum antibiotics will increase the incidence of nosocomial infection in ICU patients.

Research motivation

To explore the causes of nosocomial infection of multi drug resistant bacteria in ICU,and to provide basis for the prevention and control of nosocomial infection in ICU.

Research objectives

To provide basis for the prevention and control of nosocomial infection in ICU.

Research methods

BD PhoenixTM100 automatic bacterial identification and analysis instrument was used for cell identification.Inclusion criteria were:(1)The etiological diagnosis was multidrug-resistant bacterial infection;and(2)Inpatients in the ICU.Exclusion criteria were:(1)Diagnosis of multidrug-resistant bacterial colonization without clinical infection symptoms;(2)Contaminated samples of multidrug-resistant bacteria;and(3)Natural resistant strains.Retrospective analysis was used to investigate and collect patient records and test data.Logistic regression analysis was used to perform univariate and multivariate analyses for independent risk factors for multidrug-resistant infection.

Mistress widow! said the shirt-collar, dear mistress widow! I am becoming another man, all my creases6 are coming out; you are burning a hole in me! Ugh! Stop, I implore7 you! You rag! said the iron, travelling proudly over the shirt-collar, for it thought it was a steam engine and ought to be at the station drawing trucks

Research results

(1)Sample collection:The causative pathogens were mainly collected from sputum in 1139 cases(55.02%),blood in 521(25.17%),and drainage in 117(5.65%)(Table 1);(2)Distribution of pathogenic bacterial:()was most common strain,accounting for 35.97%(378/1051)of the total strains,followed by()(24.74%),()(21.79%)and()(9.42%).()was the most common Gram-positive bacteria strain with 8.09%(85/1051)(Table 2);(3)Drug-resistance trends and analysis of main pathogens:Resistance rates ofto minocycline in 2017 and 2019 were 28.41% and 32.42%,respectively.Resistance rates of this strain to other antimicrobials were ＞ 40%(Table 3).Energy allocation rate to the antimicrobial drug meropenem was 74.6%,and imipenem resistance rate was 75.66%(Table 4);:Analysis of 2019 data showed 21.4%(5/22)rate of resistance against cefotaxime and 13.6%(3/22)against tobramycin(Table 4).Resistance rate ofagainst meroxifen was 14.41%(33/229),whereas resistance rate against imipenem was 15.28%(35/229)(Table 3);:Analysis of 2016,2018 and 2019 data showed that a variety of antibiotics showed good antibacterial activity against(Table 4).Energy allocation rate of meropenem againstin the previous 4 years was 20.38%(53/260),whereas imipenem resistance rate was 26.5%(68/260)(Table 3);:Analysis of 2019 data showed thatwas 12.5% resistant to cefoperazone/sulbactam(3/27).Drug resistance againstin 2019 was severe compared with previous years(Table 4).Resistance rate ofto meropenem in the previous 4 years was 20.20%(20/99),whereas resistance rate ofto imipenem was 19.9%(19/99)(Table 3);:Incidence of methicillin resistance ofat the time of the study was 64.71%(55/85)(Table 3).And(4)Logistic regression analysis:A ratio of 1:1 was used to analyze risk factors for multidrug-resistant bacterial infection in 208 patients hospitalized in ICU with nosocomial infection.In addition,208 patients hospitalized at the same time,and with comparable age,sex and symptoms were selected as a control group.Factors with≤ 0.05 were included in the logistic regression model to avoid the influence of confounding factors.Logistic regression analysis showed that mechanical ventilation and urine tube intubation were risk factors for infection with multidrug-resistant bacteria(Tables 5 and 6).

Research conclusions

Although bacteria have their own drug-resistance mechanism,the primary reason for high incidence of multidrug-resistant bacteria infection in ICUs is inappropriate use of antibiotics,especially abuse of third-generation cephalosporins.Studies have reported that nosocomial infection in ICU patients is a major source of mortality.The purpose of this study was to explore and analyze the main pathogens of ICU nosocomial infections and their drug resistance.The study reports on main pathogenic bacteria of nosocomial infection and corresponding mechanism of drug resistance in the ICU at a specific time,and analyzed drug resistance of pathogenic bacteria after use of antibiotics in the same period.

Research perspectives

infection in ICU patients is often serious,accompanied by multiorgan dysfunction and serious immune dysfunction.The rapid increase of infections caused byandhas become the current concern[6].Previous studies have reported that uncontrolled use and abuse of carbapenem,third-and fourth-generation cephalosporins and quinolone antibiotics are independent risk factors for high incidence of multidrug-resistant bacteria[7].Moreover,the strains showed high sensitivity to cefoperazone/sulbactam,amikacin,and piperacillin/tazobactam.Analysis of 2019 data showed that resistance rate ofto cefotaxime and tobramycin was lower compared with previous years.These findings provide an important basis for hospital clinicians for choosing antibiotics.Hospital Enterobacteriaceae are used to study drug resistance of a variety of antimicrobials and rational use of antibiotics in clinical treatment.

ACKNOWLEDGEMENTS

:In 2017,was generally resistant to a variety of antibiotics such as piperacillin/tazobactam,aminoglycosides,quinolones and carbapenem.Analysis of 2016,2018 and 2019 data showed that a variety of antibiotics showed good antibacterial activity against(Table 4).Energy allocation rate of Meropenem againstin the previous 4 years was 20.38%(53/260),whereas imipenem resistance rate was 26.5%(68/260)(Table 3).

FOOTNOTES

1872FAIRY TALES OF HANS CHRISTIAN1 ANDERSENDELAYING IS NOT FORGETTINGby Hans Christian AndersenTHERE was an old mansion2 surrounded by a marshy3 ditch with adrawbridge which was but seldom let down:- not all guests are goodpeople. Under the roof were loopholes to shoot through, and to pourdown boiling water or even molten lead on the enemy, should heapproach. Inside the house the rooms were very high and had ceilingsof beams, and that was very useful considering the great deal of smoke which rose up from the chimney fire where the large, damp logs of wood smouldered. On the walls hung pictures of knights4 in armour5 and proud ladies in gorgeous dresses; the most stately of all walked about alive. She was called Meta Mogen; she was the mistress of the house, to her belonged the castle.

designed the study;Han Y,Zhang J,Zhang HZ,Wang YM,Zhang XY and Zhou XL studied;Zhang J and Zhang HZ analyze data and write articles;all authors have read and approved the final manuscript.

I made my decision there and then. I took my leave, and traveled away from the city. When I returned I had bought myself a cane and wrapped my leg tightly with bandages. I told everyone I had been in a car crash and that my leg would never completely heal again. My dancing days were over. No one suspected the story—I had learned to limp convincingly before I returned home. And I made sure the first person to hear of my accident was a reporter I knew well. Then I traveled to the hospital. They had pushed your grandfather outside in his wheelchair. There was a cane on the ground by his wheelchair. I took a deep breath, leaned on my cane and limped to him.

The study was reviewed and approved by the Affiliated Hospital of Hebei University Institutional Review Board(Approval No.HDFY-LL-2020-021).

Informed written consent was obtained from the patient.

So one day as Prince Fickle rode by she said to her little calf: Kneel, little calf, kneel; Be faithful and leal, Not like Prince Fickle, Who once on a time Left his poor Helena Under the lime

Han Y has received fees for serving as a speaker,Han Y has received research funding from Hebei Provincial Department of Health and Baoding science and technology;Han Y,Zhang HZ,Wang YM,Zhang XY,Zhang J,Zhou XL owns stocks and/or shares in Affiliated Hospital of Hebei University.

Corresponding author at hanyingsci@126.com.Participants gave informed consent for data sharing.

The authors have read the STROBE Statement—checklist of items,and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See:http://creativecommons.org/Licenses/by-nc/4.0/

China

Ying Han 0000-0001-7583-3697;Jin Zhang 0000-0001-7583-3697;Hong-Ze Zhang 0000-0002-8094-4233;Xin-Ying Zhang 0000-0003-4748-0390;Ya-Mei Wang 0000-0001-6920-873X.

Wu YXJ

A

Then she sat down to her work once more and span on, and as she did so an old saying which, she had often heard her godmother repeat whilst at work, came into her head, and she began to sing: Spindle, spindle, go and see, If my love will come to me

So she seated herself on his back, and they did go so swiftly! When they got there, the East Wind went in and said that the girl whom he had brought was the one who ought to have had the Prince up at the castle which lay east of the sun and west of the moon, and that now she was traveling about to find him again, so he had come there with her, and would like to hear if the West Wind knew whereabout the castle was

Wu YXJ